, This work was supported by Institut National de la Santé et de la Recherche 476

. Médicale, Centre National de la Recherche Scientifique, p.477

. Lyon, Université Claude Bernard Lyon-1 (UCBL-1), and by the Center for Molecular Medicine 478

. Cologne, BMBF (Professorinnenprogramm II, p.479

, notably grant number #14806 to A.S. and H.B., #18030 480 to S.A, and a PhD fellowship #21354 to L.D and by PhD program from la Région Rhône-Alpes to A, Association Française contre les Myopathies (AFM)

A. R. ;-l.d, L. A. , and L. A. , performed experiments and contributed to writing of the manuscript

M. O. Ngs, S. A. , and H. B. , conceived and designed the study, supervised work, acquired grants, 486 and wrote the manuscript

, References 1

M. Salganik, M. L. Hirsch, and R. J. Samulski, Adeno-associated Virus as a Mammalian DNA Vector, Microbiol Spectr, vol.3, 2015.

R. Popa-wagner, Impact of VP1-specific protein sequence motifs on adenoassociated virus type 2 intracellular trafficking and nuclear entry, J Virol, vol.86, pp.9163-9174, 2012.

F. Sonntag, S. Bleker, B. Leuchs, R. Fischer, and J. A. Kleinschmidt, Adeno-associated virus type 2 capsids with externalized VP1/VP2 trafficking domains are generated prior to passage through the cytoplasm and are maintained until uncoating occurs in the nucleus, J Virol, vol.80, pp.11040-11054, 2006.

Q. Xie, The atomic structure of adeno-associated virus (AAV-2), a vector for human gene therapy, Proc Natl Acad Sci U S A, vol.99, pp.10405-10410, 2002.

M. A. Dimattia, Structural insight into the unique properties of adeno-associated virus serotype 9, J Virol, vol.86, pp.6947-6958, 2012.

L. Govindasamy, Structurally mapping the diverse phenotype of adeno-associated virus serotype 4, J Virol, vol.80, pp.11556-11570, 2006.

B. L. Gurda, Capsid antibodies to different adeno-associated virus serotypes bind common regions, J Virol, vol.87, pp.9111-9124, 2013.

B. L. Gurda, Mapping a neutralizing epitope onto the capsid of adeno-associated virus serotype 8, J Virol, vol.86, pp.7739-7751, 2012.

H. J. Nam, Structural studies of adeno-associated virus serotype 8 capsid transitions associated with endosomal trafficking, J Virol, vol.85, pp.11791-11799, 2011.

R. Ng, Structural characterization of the dual glycan binding adeno-associated virus serotype 6, J Virol, vol.84, pp.12945-12957, 2010.

Y. S. Tseng and M. Agbandje-mckenna, Mapping the AAV Capsid Host Antibody Response toward the Development of Second Generation Gene Delivery Vectors, Front Immunol, vol.5, 2014.

K. Jooss, Y. Yang, K. J. Fisher, and J. M. Wilson, Transduction of dendritic cells by DNA viral vectors directs the immune response to transgene products in muscle fibers

, J Virol, vol.72, pp.4212-4223, 1998.

J. Zhu, X. Huang, and Y. Yang, The TLR9-MyD88 pathway is critical for adaptive immune responses to adeno-associated virus gene therapy vectors in mice, J Clin Invest, vol.119, pp.2388-2398, 2009.

K. Nieto and A. Salvetti, AAV Vectors Vaccines Against Infectious Diseases, Front Immunol, vol.5, 2014.
URL : https://hal.archives-ouvertes.fr/hal-00965088

P. Colella, G. Ronzitti, and F. Mingozzi, Emerging Issues in AAV-Mediated In Vivo Gene Therapy, Mol Ther Methods Clin Dev, vol.8, pp.87-104, 2018.
URL : https://hal.archives-ouvertes.fr/hal-01812088

A. Alloatti, F. Kotsias, J. G. Magallhaes, and S. Amigorena, Dendritic cell maturation and cross-presentation: timing matters, Immunological Reviews, vol.272, pp.97-108, 2016.

M. Merad, P. Sathe, J. Helft, J. Miller, and A. Mortha, The dendritic cell lineage: ontogeny and function of dendritic cells and their subsets in the steady state and the inflamed setting, Annu Rev Immunol, vol.31, pp.563-604, 2013.

B. Pulendran, The varieties of immunological experience: of pathogens, stress, and dendritic cells, Annu Rev Immunol, vol.33, pp.563-606, 2015.

A. Savina and S. Amigorena, Phagocytosis and antigen presentation in dendritic cells

, Immunol Rev, vol.219, pp.143-156, 2007.

G. L. Rogers, Plasmacytoid and conventional dendritic cells cooperate in crosspriming AAV capsid-specific CD8(+) T cells, Blood, vol.129, pp.3184-3195, 2017.

J. Pandya, L. Ortiz, C. Ling, A. E. Rivers, and G. Aslanidi, Rationally designed capsid and transgene cassette of AAV6 vectors for dendritic cell-based cancer immunotherapy

, Immunol Cell Biol, vol.92, pp.116-123, 2014.

L. Perabo, In vitro selection of viral vectors with modified tropism: the adenoassociated virus display, Mol Ther, vol.8, pp.151-157, 2003.

A. Kern, Identification of a heparin-binding motif on adeno-associated virus type 2 capsids, J Virol, vol.77, pp.11072-11081, 2003.

S. R. Opie, K. H. Warrington, . Jr, M. Agbandje-mckenna, and S. Zolotukhin,

N. Muzyczka, Identification of amino acid residues in the capsid proteins of adenoassociated virus type 2 that contribute to heparan sulfate proteoglycan binding, J Virol, vol.77, pp.6995-7006, 2003.

L. Perabo, Heparan sulfate proteoglycan binding properties of adeno-associated virus retargeting mutants and consequences for their in vivo tropism, J Virol, vol.80, pp.7265-7269, 2006.

J. Sallach, Tropism-modified AAV vectors overcome barriers to successful cutaneous therapy, Mol Ther, vol.22, pp.929-939, 2014.

E. D. Horowitz, Biophysical and ultrastructural characterization of adenoassociated virus capsid uncoating and genome release, J Virol, vol.87, pp.2994-3002, 2013.

J. Barnaud, Characterization of AAV vector particles stability at the single capsid level, J. Biol, 2018.

S. Adriouch, Improved Immunological Tolerance Following Combination Therapy with CTLA-4/Ig and AAV-Mediated PD-L1/2 Muscle Gene Transfer, Front Microbiol, vol.2, 2011.

R. Hardet, Oral-tolerization Prevents Immune Responses and Improves Transgene Persistence Following Gene Transfer Mediated by Adeno-associated Viral Vector, Mol Ther, vol.24, pp.87-95, 2016.
URL : https://hal.archives-ouvertes.fr/hal-02377462

M. Dalod, R. Chelbi, B. Malissen, and T. Lawrence, Dendritic cell maturation: functional specialization through signaling specificity and transcriptional programming

, EMBO J, vol.33, pp.1104-1116, 2014.

S. E. Autenrieth, Profiling of primary peripheral blood-and monocyte-derived dendritic cells using monoclonal antibodies from the HLDA10 Workshop in

A. Wollongong, Clin Transl Immunology, vol.4, 2015.

K. Schinnerling, P. Garcia-gonzalez, and J. C. Aguillon, Gene expression profiling of human monocyte-derived dendritic cells -searching for molecular regulators of tolerogenicity, frontiers in Immunology, vol.6, 2015.

C. Hotta, H. Fujimaki, M. Yoshinari, M. Nakazawa, and M. Minami, The delivery of an antigen from the endocytic compartment into the cytosol for cross-presentation is restricted to early immature dendritic cells, Immunology, vol.117, pp.97-107, 2006.

Y. Wegrowski, Cell surface proteoglycan expression during maturation of human monocytes-derived dendritic cells and macrophages, Clin Exp Immunol, vol.144, pp.485-493, 2006.

C. Summerford, J. S. Bartlett, and R. J. Samulski, AlphaVbeta5 integrin a co-receptor for adeno-associated virus type 2 infection, Nature Medicine, vol.5, pp.78-82, 1999.

H. C. Levy, Heparin binding induces conformational changes in Adeno-associated virus serotype 2, J Struct Biol, vol.165, pp.146-156, 2009.

J. O'donnell, K. A. Taylor, and M. S. Chapman, Adeno-associated virus-2 and its primary cellular receptor--Cryo-EM structure of a heparin complex, Virology, vol.385, pp.434-443, 2009.

H. Buning, A. Huber, L. Zhang, N. Meumann, and U. Hacker, Engineering the AAV capsid to optimize vector-host-interactions, Curr Opin Pharmacol, vol.24, pp.94-104, 2015.

S. Sandgren, F. Cheng, and M. Belting, Nuclear targeting of macromolecular polyanions by an HIV-Tat derived peptide. Role for cell-surface proteoglycans, J Biol Chem, vol.277, pp.38877-38883, 2002.

M. D. Stewart and R. D. Sanderson, Heparan sulfate in the nucleus and its control of cellular functions, Matrix Biol, vol.35, pp.56-59, 2014.

U. Greber, Signalling in viral entry, Cell. Mol. Life Sci, vol.59, pp.608-626, 2002.

M. Nonnenmacher and T. Weber, Adeno-Associated Virus 2 Infection Requires Endocytosis through the CLIC/GEEC Pathway, Cell Host & Microbe, vol.10, pp.563-576, 2011.

M. Nonnenmacher and T. Weber, Intracellular transport of recombinant adenoassociated virus vectors, Gene Therapy, pp.1-10, 2012.

J. W. Flatt and U. F. Greber, Viral mechanisms for docking and delivering at nuclear pore complexes, Semin Cell Dev Biol, vol.68, pp.59-71, 2017.

A. Girod, The VP1 capsid protein of adeno-associated virus type 2 is carrying a phospholipase A2 domain required for virus infectivity, J Gen Virol, vol.83, pp.973-978, 2002.

S. Stahnke, Intrinsic phospholipase A2 activity of adeno-associated virus is involved in endosomal escape of incoming particles, Virology, vol.409, pp.77-83, 2011.

A. Savina, NOX2 controls phagosomal pH to regulate antigen processing during crosspresentation by dendritic cells, Cell, vol.126, pp.205-218, 2006.

S. B. Drutman and E. S. Trombetta, Dendritic cells continue to capture and present antigens after maturation in vivo, J Immunol, vol.185, pp.2140-2146, 2010.

C. Langlet, CD64 expression distinguishes monocyte-derived and conventional dendritic cells and reveals their distinct role during intramuscular immunization, J Immunol, vol.188, pp.1751-1760, 2012.
URL : https://hal.archives-ouvertes.fr/hal-00685822

L. Arnold, Inflammatory monocytes recruited after skeletal muscle injury switch into antiinflammatory macrophages to support myogenesis, J Exp Med, vol.204, pp.1057-1069, 2007.
URL : https://hal.archives-ouvertes.fr/inserm-00136917

A. Ghenassia, Intradermal Immunization with rAAV1 Vector Induces Robust Memory CD8(+) T Cell Responses Independently of Transgene Expression in DCs, Mol Ther, vol.25, pp.2309-2322, 2017.

S. A. Nicklin, Efficient and selective AAV2-mediated gene transfer directed to human vascular endothelial cells, Mol Ther, vol.4, pp.174-181, 2001.

A. Salvetti, Factors influencing recombinant adeno-associated virus production

, Hum Gene Ther, vol.9, pp.695-706, 1998.

S. Zolotukhin, Production and purification of serotype 1, 2, and 5 recombinant adeno-associated viral vectors, Methods, vol.28, pp.158-167, 2002.

N. Alazard-dany, Definition of herpes simplex virus type 1 helper activities for adeno-associated virus early replication events, PLoS Pathog, vol.5, p.1000340, 2009.
URL : https://hal.archives-ouvertes.fr/hal-00425125

A. Wistuba, A. Kern, S. Weger, D. Grimm, and J. A. Kleinschmidt, Subcellular compartmentalization of adeno-associated virus type 2 assembly, J Virol, vol.71, pp.1341-1352, 1997.

. Vii-references and . Bibliographiques,

S. Adriouch, E. Franck, L. Drouot, C. Bonneau, N. Jolinon et al., Improved Immunological Tolerance Following Combination Therapy with CTLA-4/Ig and AAV, 2011.

, Muscle Gene Transfer. Front. Microbiol, vol.2

R. W. Atchison, B. C. Casto, and W. M. Hammon, Adenovirus-Associated Defective Virus Particles, Science, vol.149, pp.754-755, 1965.

M. F. Bachmann, G. Köhler, B. Ecabert, T. W. Mak, and M. Kopf, Cutting edge: lymphoproliferative disease in the absence of CTLA-4 is not T cell autonomous, J. Immunol. Baltim. Md, vol.163, pp.1128-1131, 1950.

B. Balakrishnan and G. R. Jayandharan, Basic biology of adeno-associated virus (AAV) vectors used in gene therapy, Curr. Gene Ther, vol.14, pp.86-100, 2014.

A. B. Balazs, J. Chen, C. M. Hong, D. S. Rao, L. Yang et al., Antibody-based Protection Against HIV Infection by Vectored ImmunoProphylaxis, Nature, vol.481, pp.81-84, 2011.

M. L. Baroja, D. Luxenberg, T. Chau, V. Ling, C. A. Strathdee et al., The Inhibitory Function of CTLA-4 Does Not Require Its Tyrosine Phosphorylation, J. Immunol, vol.164, pp.49-55, 2000.

J. S. Bartlett, R. Wilcher, and R. J. Samulski, Infectious entry pathway of adeno-associated virus and adeno-associated virus vectors, J. Virol, vol.74, pp.2777-2785, 2000.

C. L. Bennett, J. Christie, F. Ramsdell, M. E. Brunkow, P. J. Ferguson et al., The immune dysregulation, polyendocrinopathy, enteropathy, Xlinked syndrome (IPEX) is caused by mutations of FOXP3, Nat. Genet, vol.27, pp.20-21, 2001.

P. Bhatt, N. Khatri, M. Kumar, D. Baradia, and A. Misra, Microbeads mediated oral plasmid DNA delivery using polymethacrylate vectors: an effectual groundwork for colorectal cancer, Drug Deliv, vol.22, pp.849-861, 2015.

M. Biswas, D. Sarkar, S. R. Kumar, S. Nayak, G. L. Rogers et al., Synergy between rapamycin and FLT3 ligand enhances plasmacytoid dendritic celldependent induction of CD4+CD25+FoxP3+ Treg, vol.125, pp.2937-2947, 2015.

N. K. Björkström, E. Kekäläinen, and J. Mjösberg, Tissue-specific effector functions of innate lymphoid cells, Immunology, vol.139, pp.416-427, 2013.

F. Borriello, M. P. Sethna, S. D. Boyd, A. N. Schweitzer, E. A. Tivol et al., B7-1 and B7-2 Have Overlapping, Critical Roles in Immunoglobulin Class Switching and Germinal Center Formation. Immunity, vol.6, pp.303-313, 1997.

G. Borsellino, M. Kleinewietfeld, D. D. Mitri, A. Sternjak, A. Diamantini et al., Expression of ectonucleotidase CD39 by Foxp3+ Treg cells: hydrolysis of extracellular ATP and immune suppression, Blood, vol.110, pp.1225-1232, 2007.

M. L. Brantly, J. D. Chulay, L. Wang, C. Mueller, M. Humphries et al., Sustained transgene expression despite T lymphocyte responses in a clinical trial of rAAV1-AAT gene therapy, Proc. Natl. Acad. Sci. U. S. A, vol.106, pp.16363-16368, 2009.

T. V. Brennan, Y. , and Y. , PD-L1 serves as a double agent in separating GVL from GVHD, J. Clin. Invest, vol.127, pp.1627-1630

D. G. Brockstedt, G. M. Podsakoff, L. Fong, G. Kurtzman, W. Mueller-ruchholtz et al., Induction of immunity to antigens expressed by recombinant adeno-associated virus depends on the route of administration, Clin. Immunol. Orlando Fla, vol.92, pp.67-75, 1999.

J. F. Brunet, F. Denizot, M. F. Luciani, M. Roux-dosseto, M. Suzan et al., A new member of the immunoglobulin superfamily--CTLA-4, Nature, vol.328, pp.267-270, 1987.

R. M. Buller, J. E. Janik, E. D. Sebring, and J. A. Rose, Herpes Simplex Virus Types 1 and 2 Completely Help Adenovirus-Associated Virus Replication, J. Virol, vol.40, pp.241-247, 1981.

M. J. Butte, M. E. Keir, T. B. Phamduy, A. H. Sharpe, and G. J. Freeman, Programmed death-1 ligand 1 interacts specifically with the B7-1 costimulatory molecule to inhibit T cell responses, Immunity, vol.27, pp.111-122, 2007.

S. Calbo, H. Delagrèverie, C. Arnoult, F. Authier, F. Tron et al., Functional Tolerance of CD8+ T Cells Induced by Muscle-Specific Antigen Expression, J. Immunol, vol.181, pp.408-417, 2008.

R. Calcedo and J. M. Wilson, Humoral Immune Response to AAV. Front, 2013.

R. Calcedo, L. H. Vandenberghe, G. Gao, J. Lin, and J. M. Wilson, Worldwide Epidemiology of Neutralizing Antibodies to Adeno-Associated Viruses, J. Infect. Dis, vol.199, pp.381-390, 2009.

R. Calcedo, J. Franco, Q. Qin, D. W. Richardson, J. B. Mason et al., , 2015.

, Preexisting Neutralizing Antibodies to Adeno-Associated Virus Capsids in Large Animals Other Than Monkeys May Confound In Vivo Gene Therapy Studies. Hum, Gene Ther. Methods, vol.26, pp.103-105

M. Carpentier, S. Lorain, P. Chappert, M. Lalfer, R. Hardet et al., Intrinsic Transgene Immunogenicity Gears CD8+ T-cell Priming After rAAVMediated Muscle Gene Transfer, Mol. Ther, vol.23, pp.697-706, 2015.

B. M. Carreno, F. Bennett, T. A. Chau, V. Ling, D. Luxenberg et al., CTLA-4 (CD152) Can Inhibit T Cell Activation by Two Different Mechanisms Depending on Its Level of Cell Surface Expression, J. Immunol, vol.165, pp.1352-1356, 2000.

M. Cavazzana-calvo, S. Hacein-bey, G. Basile, S. De, F. Gross et al., Gene Therapy of Human Severe Combined Immunodeficiency (SCID)-X1 Disease, vol.288, pp.669-672, 2000.

S. Cecchini, T. Virag, and R. M. Kotin, Reproducible High Yields of Recombinant Adeno-Associated Virus Produced Using Invertebrate Cells in 0.02-to 200-Liter Cultures, Hum. Gene Ther, vol.22, pp.1021-1030, 2011.

L. Charbonnier, B. Vokaer, P. H. Lemaître, K. A. Field, O. Leo et al., CTLA4-Ig Restores Rejection of MHC Class-II Mismatched Allografts by Disabling IL-2-Expanded Regulatory T Cells, Am. J. Transplant, vol.12, pp.2313-2321, 2012.

A. Chaudhri, Y. Xiao, B. Zhu, and G. J. Freeman, PD-L1 binds with B7-1 only in cis on the same cell surface, J. Immunol, vol.198, 2017.

A. Chaudhri, Y. Xiao, A. N. Klee, X. Wang, B. Zhu et al., PD-L1 Binds to B7-1 Only In Cis on the Same Cell Surface, Cancer Immunol. Res, vol.6, pp.921-929, 2018.

W. Chen, W. Jin, and S. M. Wahl, Engagement of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) induces transforming growth factor beta (TGF-beta) production by murine CD4(+) T cells, J. Exp. Med, vol.188, pp.1849-1857, 1998.

W. Chen, W. Jin, N. Hardegen, K. Lei, L. Li et al., Conversion of Peripheral CD4+CD25? Naive T Cells to CD4+CD25+ Regulatory T Cells by TGF-? Induction of Transcription Factor Foxp3, J. Exp. Med, vol.198, pp.1875-1886, 2003.

X. Cheng, H. Dai, N. Wan, Y. Moore, R. Vankayalapati et al., Interaction of programmed death-1 and programmed death-1 ligand-1 contributes to testicular immune privilege, Transplantation, vol.87, pp.1778-1786, 2009.

N. Chirmule, W. Xiao, A. Truneh, M. A. Schnell, J. V. Hughes et al., , 2000.

, Humoral Immunity to Adeno-Associated Virus Type 2 Vectors following Administration to Murine and Nonhuman Primate Muscle, J. Virol, vol.74, pp.2420-2425

S. R. Choudhury, Z. Fitzpatrick, A. F. Harris, S. A. Maitland, J. S. Ferreira et al., Vivo Selection Yields AAV-B1 Capsid for Central Nervous System and Muscle Gene Therapy, vol.24, pp.1247-1257, 2016.

N. Chun, R. L. Fairchild, Y. Li, J. Liu, M. Zhang et al., Complement Dependence of Murine Costimulatory Blockade-Resistant Cellular Cardiac Allograft Rejection, Am. J. Transplant, vol.17, pp.2810-2819, 2017.

A. V. Collins, D. W. Brodie, R. J. Gilbert, A. Iaboni, R. Manso-sancho et al., The Interaction Properties of Costimulatory Molecules Revisited, Immunity, vol.17, pp.201-210, 2002.

L. W. Collison, V. Chaturvedi, A. L. Henderson, P. R. Giacomin, C. Guy et al., Interleukin-35-mediated induction of a novel regulatory T cell population, Nat. Immunol, vol.11, pp.1093-1101, 2010.

L. Cordier, A. A. Hack, M. O. Scott, E. R. Barton-davis, G. Gao et al., Rescue of Skeletal Muscles of ?-Sarcoglycan-Deficient Mice with Adeno-Associated VirusMediated Gene Transfer, Mol. Ther, vol.1, pp.119-129, 2000.

L. Cordier, G. Gao, A. A. Hack, E. M. Mcnally, J. M. Wilson et al., , 2001.

, Muscle-Specific Promoters May Be Necessary for Adeno-Associated Virus-Mediated Gene Transfer in the Treatment of Muscular Dystrophies, Hum. Gene Ther, vol.12, pp.205-215

M. Corti, B. Cleaver, N. Clément, T. J. Conlon, K. J. Faris et al., Evaluation of Readministration of a Recombinant Adeno-Associated Virus Vector Expressing Acid Alpha-Glucosidase in Pompe Disease: Preclinical to Clinical Planning, Hum. Gene Ther. Clin. Dev, vol.26, pp.185-193, 2015.

E. Cretney, A. Xin, W. Shi, M. Minnich, F. Masson et al., The transcription factors Blimp-1 and IRF4 jointly control the differentiation and function of effector regulatory T cells, Nat. Immunol, vol.12, pp.304-311, 2011.

P. J. Darlington, M. G. Kirchhof, G. Criado, J. Sondhi, and J. Madrenas, Hierarchical Regulation of CTLA-4 Dimer-Based Lattice Formation and Its Biological Relevance for T Cell Inactivation, J. Immunol, vol.175, pp.996-1004, 2005.

S. Deaglio, K. M. Dwyer, W. Gao, D. Friedman, A. Usheva et al., Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression, J. Exp. Med, vol.204, pp.1257-1265, 2007.

J. Denard, B. Marolleau, C. Jenny, T. N. Rao, H. J. Fehling et al., CReactive Protein (CRP) Is Essential for Efficient Systemic Transduction of Recombinant Adeno-Associated Virus Vector 1 (rAAV-1) and rAAV-6 in Mice, J. Virol, vol.87, pp.10784-10791, 2013.

P. Devarajan, J. Miska, J. B. Lui, D. Swieboda, C. et al., Opposing Effects of CTLA4 Insufficiency on Regulatory versus Conventional T Cells in Autoimmunity Converge on Effector Memory in Target Tissue, J. Immunol. Baltim. Md, pp.4368-4380, 2014.

S. De-zolt, F. Schnütgen, C. Seisenberger, J. Hansen, M. Hollatz et al., High-throughput trapping of secretory pathway genes in mouse embryonic stem cells, Nucleic Acids Res, vol.34, p.25, 2006.

Y. Ding, R. Han, W. Jiang, J. Xiao, H. Liu et al., Programmed Death Ligand 1 Plays a Neuroprotective Role in Experimental Autoimmune Neuritis by Controlling Peripheral Nervous System Inflammation of Rats, J. Immunol, 2016.

A. Douar, K. Poulard, D. Stockholm, and O. Danos, Intracellular Trafficking of AdenoAssociated Virus Vectors: Routing to the Late Endosomal Compartment and Proteasome Degradation, J. Virol, vol.75, pp.1824-1833, 2001.

L. F. Earley, J. M. Powers, K. Adachi, J. T. Baumgart, N. L. Meyer et al.,

, Adeno-associated Virus (AAV) Assembly-Activating Protein Is Not an Essential Requirement for Capsid Assembly of AAV Serotypes 4, 5, and 11, J. Virol, p.91

M. J. Eppihimer, J. Gunn, G. J. Freeman, E. A. Greenfield, T. Chernova et al., Expression and regulation of the PD-L1 immunoinhibitory molecule on microvascular endothelial cells, vol.9, pp.133-145, 1994.

L. Esposito, K. M. Hunter, J. Clark, D. B. Rainbow, H. Stevens et al., Investigation of Soluble and Transmembrane CTLA-4 Isoforms in Serum and Microvesicles, J. Immunol, p.1303389, 2014.

S. M. Faust, P. Bell, B. J. Cutler, S. N. Ashley, Y. Zhu et al., CpGdepleted adeno-associated virus vectors evade immune detection, J. Clin. Invest, vol.123, pp.2994-3001, 2013.

H. Fayyad-kazan, R. Rouas, M. Fayyad-kazan, R. Badran, N. El-zein et al., MicroRNA Profile of Circulating CD4-positive Regulatory T Cells in Human Adults and Impact of Differentially Expressed MicroRNAs on Expression of Two Genes Essential to Their Function, J. Biol. Chem, vol.287, pp.9910-9922, 2012.

V. Ferreira, J. Twisk, K. Kwikkers, E. Aronica, D. Brisson et al., , 2014.

, Immune Responses to Intramuscular Administration of Alipogene Tiparvovec (AAV1-LPLS447X) in a Phase II Clinical Trial of Lipoprotein Lipase Deficiency Gene Therapy. Hum, Gene Ther, vol.25, pp.180-188

P. A. Fields, V. R. Arruda, E. Armstrong, K. Chu, F. Mingozzi et al., Risk and Prevention of Anti-factor IX Formation in AAV-Mediated Gene Transfer in the Context of a Large Deletion of F9, Mol. Ther, vol.4, pp.201-210, 2001.

B. T. Fife, K. E. Pauken, T. N. Eagar, T. Obu, J. Wu et al., Interactions between PD-1 and PD-L1 promote tolerance by blocking the TCR-induced stop signal, Nat. Immunol, vol.10, pp.1185-1192, 2009.

Z. Fitzpatrick, C. Leborgne, E. Barbon, E. Masat, G. Ronzitti et al., Influence of Pre-existing Anti-capsid Neutralizing and Binding Antibodies on AAV Vector Transduction, Mol. Ther. Methods Clin. Dev, vol.9, pp.119-129, 2018.
URL : https://hal.archives-ouvertes.fr/hal-01830017

K. M. Flanigan, K. Campbell, L. Viollet, W. Wang, A. M. Gomez et al., , 2013.

T. Anti-dystrophin, Cell Responses in Duchenne Muscular Dystrophy: Prevalence and a Glucocorticoid Treatment Effect. Hum. Gene Ther, vol.24, pp.797-806

J. D. Fontenot, J. P. Rasmussen, L. M. Williams, J. L. Dooley, A. G. Farr et al., , 2005.

, Regulatory T Cell Lineage Specification by the Forkhead Transcription Factor Foxp3, Immunity, vol.22, pp.329-341

L. M. Francisco, V. H. Salinas, K. E. Brown, V. K. Vanguri, G. J. Freeman et al., PD-L1 regulates the development, maintenance, and function of induced regulatory T cells, J. Exp. Med, vol.206, pp.3015-3029, 2009.

A. S. Freedman, G. Freeman, J. C. Horowitz, J. Daley, and L. M. Nadler, B7, a B-cell-restricted antigen that identifies preactivated B cells, J. Immunol, vol.139, pp.3260-3267, 1987.

G. J. Freeman, J. G. Gribben, V. A. Boussiotis, J. W. Ng, V. A. Restivo et al., Cloning of B7-2: a CTLA-4 counter-receptor that costimulates human T cell proliferation, Science, vol.262, pp.909-911, 1993.

G. J. Freeman, A. J. Long, Y. Iwai, K. Bourque, T. Chernova et al., Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation, J. Exp. Med, vol.192, pp.1027-1034, 2000.

C. A. Fuhrman, W. Yeh, H. R. Seay, P. S. Lakshmi, G. Chopra et al., Divergent phenotypes of human regulatory T cells expressing the receptors TIGIT and CD226, J. Immunol. Baltim. Md, pp.145-155, 2015.

G. Gao, L. H. Vandenberghe, and J. M. Wilson, New recombinant serotypes of AAV vectors, Curr. Gene Ther, vol.5, pp.285-297, 2005.

G. Gao, M. R. Alvira, L. Wang, R. Calcedo, J. Johnston et al., Novel adenoassociated viruses from rhesus monkeys as vectors for human gene therapy, Proc. Natl. Acad. Sci. U. S. A, vol.99, pp.11854-11859, 2002.

A. Ghenassia, D. Gross, S. Lorain, F. Tros, D. Urbain et al., Intradermal Immunization with rAAV1 Vector Induces Robust Memory CD8+ T Cell Responses Independently of Transgene Expression in DCs, Mol. Ther, vol.25, pp.2309-2322, 2017.

V. Ghetie, S. Popov, J. Borvak, C. Radu, D. Matesoi et al., Increasing the serum persistence of an IgG fragment by random mutagenesis, Nat. Biotechnol, vol.15, pp.637-640, 1997.

M. Gilliet, W. Cao, and Y. Liu, Plasmacytoid dendritic cells: sensing nucleic acids in viral infection and autoimmune diseases, Nat. Rev. Immunol, vol.8, pp.594-606, 2008.

D. C. Gondek, V. Devries, E. C. Nowak, L. Lu, K. A. Bennett et al., , 2008.

, Transplantation Survival Is Maintained by Granzyme B+ Regulatory Cells and Adaptive Regulatory T Cells, J. Immunol, vol.181, pp.4752-4760

J. M. Green, P. J. Noel, A. I. Sperling, T. L. Walunas, G. S. Gray et al., Absence of B7-dependent responses in CD28-deficient mice, Immunity, vol.1, pp.501-508, 1994.

J. C. Grieger, S. M. Soltys, and R. J. Samulski, Production of Recombinant Adeno-associated Virus Vectors Using Suspension HEK293 Cells and Continuous Harvest of Vector From the Culture Media for GMP FIX and FLT1 Clinical Vector, Mol. Ther. J. Am. Soc. Gene Ther, vol.24, pp.287-297, 2016.

U. Grohmann, C. Orabona, F. Fallarino, C. Vacca, F. Calcinaro et al., CTLA-4-Ig regulates tryptophan catabolism in vivo, Nat. Immunol, vol.3, pp.1097-1101, 2002.

P. Gu, J. Fang-gao, C. A. Souza, A. Kowalczyk, K. Chou et al., Trogocytosis of CD80 and CD86 by induced regulatory T cells, Cell. Mol. Immunol, vol.9, pp.136-146, 2012.

F. Guo, C. Iclozan, W. Suh, C. Anasetti, Y. et al., CD28 Controls Differentiation of Regulatory T Cells from Naive CD4 T Cells, J. Immunol. Baltim. Md, vol.181, pp.2285-2291, 1950.

B. György, C. Sage, A. A. Indzhykulian, D. I. Scheffer, A. R. Brisson et al., Rescue of Hearing by Gene Delivery to Inner-Ear Hair Cells Using Exosome-Associated AAV, Mol. Ther, vol.25, pp.379-391, 2017.

S. Hacein-bey-abina, C. V. Kalle, M. Schmidt, M. P. Mccormack, N. Wulffraat et al., LMO2-Associated Clonal T Cell Proliferation in Two Patients after Gene Therapy for SCID-X1, Science, vol.302, pp.415-419, 2003.

R. J. Hajjar, K. Zsebo, L. Deckelbaum, C. Thompson, J. Rudy et al., Design of a phase 1/2 trial of intracoronary administration of AAV1/SERCA2a in patients with heart failure, J. Card. Fail, vol.14, pp.355-367, 2008.

C. L. Halbert, T. A. Standaert, C. B. Wilson, and A. D. Miller, Successful Readministration of AdenoAssociated Virus Vectors to the Mouse Lung Requires Transient Immunosuppression during the Initial Exposure, J. Virol, vol.72, pp.9795-9805, 1998.

S. Han, S. Li, E. D. Brooks, E. Masat, C. Leborgne et al., Enhanced Efficacy from Gene Therapy in Pompe Disease Using Coreceptor Blockade, Hum. Gene Ther, vol.26, pp.26-35, 2015.

J. Hansen, K. Qing, and A. Srivastava, Infection of Purified Nuclei by Adeno-associated Virus 2, Mol. Ther, vol.4, pp.289-296, 2001.

R. Hardet, B. Chevalier, L. Dupaty, Y. Naïmi, G. Riou et al., Oral-tolerization Prevents Immune Responses and Improves Transgene Persistence Following Gene Transfer Mediated by Adeno-associated Viral Vector, Mol. Ther, vol.24, pp.87-95, 2016.

K. Harper, C. Balzano, E. Rouvier, M. G. Mattéi, M. F. Luciani et al., CTLA-4 and CD28 activated lymphocyte molecules are closely related in both mouse and human as to sequence, message expression, gene structure, and chromosomal location, J. Immunol, vol.147, pp.1037-1044, 1991.

S. Haxhinasto, D. Mathis, and C. Benoist, The AKT-mTOR axis regulates de novo differentiation of CD4+Foxp3+ cells, J. Exp. Med, vol.205, pp.565-574, 2008.

P. L. Hermonat, Down-regulation of the human c-fos and c-myc proto-oncogene promoters by adeno-associated virus Rep78, Cancer Lett, vol.81, pp.129-136, 1994.

A. Herrmann, S. Grosse, K. Börner, C. Krämer, E. Wiedtke et al., Impact of the assembly-activating protein (AAP) on molecular evolution of synthetic Adeno-associated virus (AAV) capsids. Hum, Gene Ther, 2018.

R. W. Herzog, J. N. Hagstrom, S. Kung, S. J. Tai, J. M. Wilson et al., Stable gene transfer and expression of human blood coagulation factor IX after intramuscular injection of recombinant adeno-associated virus, Proc. Natl. Acad. Sci. U. S. A, vol.94, pp.5804-5809, 1997.

R. W. Herzog, J. D. Mount, V. R. Arruda, K. A. High, and C. D. Lothrop, Muscle-Directed Gene Transfer and Transient Immune Suppression Result in Sustained Partial Correction of Canine Hemophilia B Caused by a Null Mutation, Mol. Ther, vol.4, pp.192-200, 2001.

R. W. Herzog, P. A. Fields, V. R. Arruda, J. O. Brubaker, E. Armstrong et al., Influence of Vector Dose on Factor IX-Specific T and B Cell Responses in Muscle-Directed Gene Therapy, Hum. Gene Ther, vol.13, pp.1281-1291, 2002.

F. S. Hodi, S. J. O'day, D. F. Mcdermott, R. W. Weber, J. A. Sosman et al., Improved Survival with Ipilimumab in Patients with Metastatic Melanoma, N. Engl. J. Med, vol.363, pp.711-723, 2010.

B. E. Hoffman, E. Dobrzynski, L. Wang, L. Hirao, F. Mingozzi et al., Muscle as a Target for Supplementary Factor IX Gene Transfer, Hum. Gene Ther, vol.18, pp.603-613, 2007.

K. Honda, Y. Ohba, H. Yanai, H. Negishi, T. Mizutani et al., , 2005.

, Spatiotemporal regulation of MyD88-IRF-7 signalling for robust type-I interferon induction, Nature, vol.434, pp.1035-1040

M. Hösel, M. Broxtermann, H. Janicki, K. Esser, S. Arzberger et al., Toll-like receptor 2-mediated innate immune response in human nonparenchymal liver cells toward adeno-associated viral vectors, Hepatology, vol.55, pp.287-297, 2012.

M. Hösel, J. Lucifora, T. Michler, G. Holz, M. Gruffaz et al., Hepatitis B virus infection enhances susceptibility toward adeno-associated viral vector transduction in vitro and in vivo, Hepatology, vol.59, pp.2110-2120, 2014.

C. Hu, R. G. Cela, M. Suzuki, B. Lee, and G. S. Lipshutz, Neonatal helper-dependent adenoviral vector gene therapy mediates correction of hemophilia A and tolerance to human factor VIII, Proc. Natl. Acad. Sci. U. S. A, vol.108, pp.2082-2087, 2011.

Y. Huang, C. Zhu, Y. Kondo, A. C. Anderson, A. Gandhi et al., CEACAM1 regulates TIM-3-mediated tolerance and exhaustion, Nature, vol.517, pp.386-390, 2015.

B. Huard, P. Prigent, M. Tournier, D. Bruniquel, and F. Triebel, CD4/major histocompatibility complex class II interaction analyzed with CD4-and lymphocyte activation gene-3 (LAG-3)-Ig fusion proteins, Eur. J. Immunol, vol.25, pp.2718-2721, 1995.

E. Hui, J. Cheung, J. Zhu, X. Su, M. J. Taylor et al., T cell costimulatory receptor CD28 is a primary target for PD-1-mediated inhibition, Science, vol.355, pp.1428-1433, 2017.

W. Ise, M. Kohyama, K. M. Nutsch, H. M. Lee, A. Suri et al., CTLA-4 suppresses the pathogenicity of self antigen-specific T cells by cell-intrinsic and cellextrinsic mechanisms, Nat. Immunol, vol.11, pp.129-135, 2010.

Y. Ishida, Y. Agata, K. Shibahara, and T. Honjo, Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death, EMBO J, vol.11, pp.3887-3895, 1992.

C. A. Janeway, Approaching the Asymptote? Evolution and Revolution in Immunology, Cold Spring Harb. Symp. Quant. Biol, vol.54, pp.1-13, 1989.

L. M. Kattenhorn, C. H. Tipper, L. Stoica, D. S. Geraghty, T. L. Wright et al., Adeno-Associated Virus Gene Therapy for Liver Disease, Hum. Gene Ther, vol.27, pp.947-961, 2016.

H. L. Kaufman, F. J. Kohlhapp, and A. Zloza, Oncolytic viruses: a new class of immunotherapy drugs, Nat. Rev. Drug Discov, vol.14, pp.642-662, 2015.

M. E. Keir, S. C. Liang, I. Guleria, Y. E. Latchman, A. Qipo et al., Tissue expression of PD-L1 mediates peripheral T cell tolerance, J. Exp. Med, vol.203, pp.883-895, 2006.

M. E. Keir, M. J. Butte, G. J. Freeman, and A. H. Sharpe, PD-1 and Its Ligands in Tolerance and Immunity, Annu. Rev. Immunol, vol.26, pp.677-704, 2008.

J. M. Kelich, J. Ma, B. Dong, Q. Wang, M. Chin et al., Superresolution imaging of nuclear import of adeno-associated virus in live cells, Mol. Ther. Methods Clin. Dev, vol.2, p.15047, 2015.

R. Khattri, J. A. Auger, M. D. Griffin, A. H. Sharpe, and J. A. Bluestone, Lymphoproliferative disorder in CTLA-4 knockout mice is characterized by CD28-regulated activation of Th2 responses, J. Immunol. Baltim. Md, vol.162, pp.5784-5791, 1950.

E. J. Kim, J. Kwun, A. C. Gibby, J. J. Hong, A. B. Farris et al., Costimulation blockade alters germinal center responses and prevents antibody-mediated rejection, Am. J. Transplant. Off. J. Am. Soc. Transplant. Am. Soc. Transpl. Surg, vol.14, pp.59-69, 2014.

J. M. Kim, J. P. Rasmussen, and A. Y. Rudensky, Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice, Nat. Immunol, vol.8, pp.191-197, 2007.

K. Klocke, S. Sakaguchi, R. Holmdahl, and K. Wing, Induction of autoimmune disease by deletion of CTLA-4 in mice in adulthood, Proc. Natl. Acad. Sci. U. S. A, vol.113, pp.2383-2392, 2016.

K. Kong, G. Fu, Y. Zhang, T. Yokosuka, J. Casas et al., Protein Kinase C-? Controls CTLA-4-Mediated Regulatory T Cell Function, Nat. Immunol, vol.15, pp.465-472, 2014.

H. Kristjansdottir, K. Steinsson, I. Gunnarsson, G. Gröndal, K. Erlendsson et al., Lower expression levels of the programmed death 1 receptor on CD4+CD25+ T cells and correlation with the PD-1.3A genotype in patients with systemic lupus erythematosus, Arthritis Rheum, vol.62, pp.1702-1711, 2010.

M. F. Krummel, A. , and J. P. , CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation, J. Exp. Med, vol.182, pp.459-465, 1995.

S. R. Kumar, B. E. Hoffman, C. Terhorst, Y. P. De-jong, and R. W. Herzog, The Balance between CD8+ T Cell-Mediated Clearance of AAV-Encoded Antigen in the Liver and Tolerance Is Dependent on the Vector Dose, Mol. Ther. J. Am. Soc. Gene Ther, vol.25, pp.880-891, 2017.

T. Kurosaki, K. Kometani, and W. Ise, Memory B cells, Nat. Rev. Immunol, vol.15, pp.149-159, 2015.

C. Leibler, A. Thiolat, C. Hénique, C. Samson, C. Pilon et al., Control of Humoral Response in Renal Transplantation by Belatacept Depends on a Direct Effect on B Cells and Impaired T Follicular Helper-B Cell Crosstalk, J. Am. Soc. Nephrol. ASN, 2018.

C. Li, S. Lim, W. Xia, H. Lee, L. Chan et al., Glycosylation and stabilization of programmed death ligand-1 suppresses T-cell activity, Nat. Commun, vol.7, p.12632, 2016.

H. Li, M. O. Lasaro, B. Jia, S. W. Lin, L. H. Haut et al., Capsid-specific T-cell Responses to Natural Infections With Adeno-associated Viruses in Humans Differ From Those of Nonhuman Primates, Mol. Ther, vol.19, pp.2021-2030, 2011.

J. Lin, R. Calcedo, L. H. Vandenberghe, P. Bell, S. Somanathan et al., A new genetic vaccine platform based on an adeno-associated virus isolated from a rhesus macaque, J. Virol, vol.83, pp.12738-12750, 2009.

P. S. Linsley and P. Golstein, Lymphocyte activation: T-cell regulation by CTLA-4, Curr. Biol, vol.6, pp.398-400, 1996.

P. S. Linsley, J. L. Greene, W. Brady, J. Bajorath, J. A. Ledbetter et al., Human B7-1 (CD80) and B7-2 (CD86) bind with similar avidities but distinct kinetics to CD28 and CTLA-4 receptors, Immunity, vol.1, pp.793-801, 1994.

L. Lisowski, A. P. Dane, K. Chu, Y. Zhang, S. C. Cunningham et al., Selection and evaluation of clinically relevant AAV variants in a xenograft liver model, Nature, vol.506, pp.382-386, 2014.

P. A. Loduca, B. E. Hoffman, and R. W. Herzog, Hepatic gene transfer as a means of tolerance induction to transgene products, Curr. Gene Ther, vol.9, pp.104-114, 2009.

S. Lorain, D. Gross, A. Goyenvalle, O. Danos, J. Davoust et al., Transient Immunomodulation Allows Repeated Injections of AAV1 and Correction of Muscular Dystrophy in Multiple Muscles, Mol. Ther, vol.16, pp.541-547, 2008.

L. Lu, X. F. Qian, J. H. Rao, X. H. Wang, S. G. Zheng et al., Rapamycin Promotes the Expansion of CD4+ Foxp3+ Regulatory T Cells After Liver Transplantation, Transplant. Proc, vol.42, pp.1755-1757, 2010.

Y. Lu, H. Schneider, and C. E. Rudd, Murine regulatory T cells differ from conventional T cells in resisting the CTLA-4 reversal of TCR stop-signal, Blood, vol.120, pp.4560-4570, 2012.

J. A. Lucas, J. Menke, W. A. Rabacal, F. J. Schoen, A. H. Sharpe et al., PD-L1 Regulates a Critical Checkpoint for Autoimmune Myocarditis and Pneumonitis in MRL mice, J. Immunol. Baltim. Md, vol.181, pp.2513-2521, 1950.

E. Lusby, K. H. Fife, and K. I. Berns, Nucleotide sequence of the inverted terminal repetition in adeno-associated virus DNA, J. Virol, vol.34, pp.402-409, 1980.

D. A. Mandelbrot, A. J. Mcadam, and A. H. Sharpe, B7-1 or B7-2 Is Required to Produce the Lymphoproliferative Phenotype in Mice Lacking Cytotoxic T Lymphocyte-associated Antigen 4 (CTLA-4), J. Exp. Med, vol.189, pp.435-440, 1999.

W. C. Manning, X. Paliard, S. Zhou, P. Bland, M. Lee et al., Genetic immunization with adeno-associated virus vectors expressing herpes simplex virus type 2 glycoproteins B and D, J. Virol, vol.71, pp.7960-7962, 1997.

C. S. Manno, G. F. Pierce, V. R. Arruda, B. Glader, M. Ragni et al., Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by the host immune response, Nat. Med, vol.12, pp.342-347, 2006.

A. T. Martino, M. Suzuki, D. M. Markusic, I. Zolotukhin, R. C. Ryals et al., The genome of self-complementary adeno-associated viral vectors increases Toll-like receptor 9-dependent innate immune responses in the liver, Blood, vol.117, pp.6459-6468, 2011.

A. T. Martino, R. W. Herzog, I. Anegon, A. , and O. , Measuring Immune Responses to recombinant AAV Gene Transfer, Methods Mol. Biol. Clifton NJ, vol.807, pp.259-272, 2011.

E. L. Masteller, E. Chuang, A. C. Mullen, S. L. Reiner, and C. B. Thompson, Structural Analysis of CTLA-4 Function In Vivo, J. Immunol, vol.164, pp.5319-5327, 2000.

D. Mathews, W. Wakwe, S. Kim, M. Lowe, C. Breeden et al., Belatacept Resistant Rejection is Associated with CD28+ Memory CD8 T cells, Am. J. Transplant. Off. J. Am. Soc. Transplant. Am. Soc. Transpl. Surg, vol.17, pp.2285-2299, 2017.

A. P. Mccaffrey, P. Fawcett, H. Nakai, R. L. Mccaffrey, A. Ehrhardt et al., The Host Response to Adenovirus, Helper-dependent Adenovirus, and Adeno-associated Virus in Mouse Liver, Mol. Ther, vol.16, pp.931-941, 2008.

D. M. Mccarty, Self-complementary AAV Vectors, Advances and Applications. Mol. Ther, vol.16, pp.1648-1656, 2008.

D. M. Mccarty, Self-complementary AAV Vectors, Advances and Applications. Mol. Ther, vol.16, pp.1648-1656, 2008.

A. L. Mellor, P. Chandler, B. Baban, A. M. Hansen, B. Marshall et al., Specific subsets of murine dendritic cells acquire potent T cell regulatory functions following CTLA4-mediated induction of indoleamine 2,3 dioxygenase, Int. Immunol, vol.16, pp.1391-1401, 2004.

J. R. Mendell, K. Campbell, L. Rodino-klapac, Z. Sahenk, C. Shilling et al., Dystrophin Immunity in Duchenne's Muscular Dystrophy, N. Engl. J. Med, vol.363, pp.1429-1437, 2010.

J. R. Mendell, L. Rodino-klapac, Z. Sahenk, V. Malik, B. K. Kaspar et al., , 2012.

, Gene Therapy for Muscular Dystrophy: Lessons Learned and Path Forward. Neurosci. Lett, vol.527, pp.90-99

J. R. Mendell, S. Al-zaidy, R. Shell, W. D. Arnold, L. R. Rodino-klapac et al., Single-Dose Gene-Replacement Therapy for Spinal Muscular Atrophy, N. Engl. J. Med, vol.377, pp.1713-1722, 2017.
DOI : 10.1056/nejmoa1706198

J. R. Mendell, S. Al-zaidy, R. Shell, W. D. Arnold, L. R. Rodino-klapac et al., Single-Dose Gene-Replacement Therapy for Spinal Muscular Atrophy, 2017.
DOI : 10.1056/nejmoa1706198

S. Mettananda, R. J. Gibbons, and D. R. Higgs, ?-Globin as a molecular target in the treatment of ?-thalassemia, Blood, vol.125, pp.3694-3701, 2015.

C. H. Miao, R. O. Snyder, D. B. Schowalter, G. A. Patijn, B. Donahue et al., The kinetics of rAAV integration in the liver, Nat. Genet, vol.19, pp.13-15, 1998.

F. Mingozzi and H. Büning, Adeno-Associated Viral Vectors at the Frontier between Tolerance and Immunity, Front. Immunol, vol.6, 2015.
DOI : 10.3389/fimmu.2015.00120

URL : https://hal.archives-ouvertes.fr/hal-01216420

F. Mingozzi, Y. Liu, E. Dobrzynski, A. Kaufhold, J. H. Liu et al., Induction of immune tolerance to coagulation factor IX antigen by in vivo hepatic gene transfer, J. Clin. Invest, vol.111, pp.1347-1356, 2003.

F. Mingozzi, J. J. Meulenberg, D. J. Hui, E. Basner-tschakarjan, N. C. Hasbrouck et al., AAV-1-mediated gene transfer to skeletal muscle in humans results in dose-dependent activation of capsid-specific T cells, Blood, vol.114, pp.2077-2086, 2009.

N. A. Mitchison, The carrier effect in the secondary response to hapten-protein conjugates. I. Measurement of the effect with transferred cells and objections to the local environment hypothesis, Eur. J. Immunol, vol.1, pp.10-17, 1971.

T. Miyazaki, A. Dierich, C. Benoist, and D. Mathis, Independent Modes of Natural Killing Distinguished in Mice Lacking Lag3, Science, vol.272, pp.405-408, 1996.

P. E. Monahan, C. D. Lothrop, J. Sun, M. L. Hirsch, T. Kafri et al., Proteasome Inhibitors Enhance Gene Delivery by AAV Virus Vectors Expressing Large Genomes in Hemophilia Mouse and Dog Models: A Strategy for Broad Clinical Application, Mol. Ther, vol.18, pp.1907-1916, 2010.

V. Monteilhet, S. Saheb, S. Boutin, C. Leborgne, P. Veron et al., A 10 Patient Case Report on the Impact of Plasmapheresis Upon Neutralizing Factors Against Adeno-associated Virus (AAV) Types 1, 2, 6, and 8, Mol. Ther, vol.19, pp.2084-2091, 2011.

M. Moskalenko, L. Chen, M. Van-roey, B. A. Donahue, R. O. Snyder et al., Epitope Mapping of Human Anti-Adeno-Associated Virus Type 2 Neutralizing Antibodies: Implications for Gene Therapy and Virus Structure, J. Virol, vol.74, pp.1761-1766, 2000.
DOI : 10.1128/jvi.74.4.1761-1766.2000

URL : https://jvi.asm.org/content/74/4/1761.full.pdf

J. D. Mount, R. W. Herzog, D. M. Tillson, S. A. Goodman, N. Robinson et al., Sustained phenotypic correction of hemophilia B dogs with a factor IX null mutation by liver-directed gene therapy, Blood, vol.99, pp.2670-2676, 2002.

C. Mueller, J. D. Chulay, B. C. Trapnell, M. Humphries, B. Carey et al., Human Treg responses allow sustained recombinant adeno-associated virus-mediated transgene expression, J. Clin. Invest, vol.123, pp.5310-5318, 2013.
DOI : 10.1172/jci70314

URL : http://www.jci.org/articles/view/70314/files/pdf

C. Mueller, G. Gernoux, A. M. Gruntman, F. Borel, E. P. Reeves et al., 5 Year Expression and Neutrophil Defect Repair after Gene Therapy in Alpha-1 Antitrypsin Deficiency, Mol. Ther, vol.25, pp.1387-1394, 2017.
DOI : 10.1016/j.ymthe.2017.03.029

URL : https://doi.org/10.1016/j.ymthe.2017.03.029

D. H. Munn, E. Shafizadeh, J. T. Attwood, I. Bondarev, A. Pashine et al., Inhibition of T Cell Proliferation by Macrophage Tryptophan Catabolism, J. Exp. Med, vol.189, pp.1363-1372, 1999.

G. Murlidharan, A. Crowther, R. A. Reardon, J. Song, A. et al., Glymphatic fluid transport controls paravascular clearance of AAV vectors from the brain, JCI Insight, vol.1, p.88034, 2016.

A. C. Nathwani, J. T. Gray, C. Y. Ng, J. Zhou, Y. Spence et al., Self-complementary adeno-associated virus vectors containing a novel liver-specific human factor IX expression cassette enable highly efficient transduction of murine and nonhuman primate liver, Blood, vol.107, pp.2653-2661, 2006.

A. C. Nathwani, E. G. Tuddenham, S. Rangarajan, C. Rosales, J. Mcintosh et al., Adenovirus-Associated Virus Vector-Mediated Gene Transfer in Hemophilia B, N. Engl. J. Med, vol.365, pp.2357-2365, 2011.

A. C. Nathwani, C. Rosales, J. Mcintosh, G. Rastegarlari, D. Nathwani et al., Long-term Safety and Efficacy Following Systemic Administration of a Self-complementary AAV Vector Encoding Human FIX Pseudotyped With Serotype 5 and 8 Capsid Proteins, Mol. Ther, vol.19, pp.876-885, 2011.

A. C. Nathwani, U. M. Reiss, E. G. Tuddenham, C. Rosales, P. Chowdary et al., Long-Term Safety and Efficacy of Factor IX Gene Therapy in Hemophilia B, N. Engl. J. Med, vol.371, 1994.

J. Nault, S. Datta, S. Imbeaud, A. Franconi, M. Mallet et al., Recurrent AAV2-related insertional mutagenesis in human hepatocellular carcinomas, Nat. Genet, vol.47, pp.1187-1193, 2015.

S. Nayak, O. Cao, B. E. Hoffman, M. Cooper, S. Zhou et al., , 2009.

, Prophylactic immune tolerance induced by changing the ratio of antigen-specific effector to regulatory T cells, J. Thromb. Haemost. JTH, vol.7, pp.1523-1532

S. C. Nicolson and R. J. Samulski, Recombinant Adeno-Associated Virus Utilizes Host Cell Nuclear Import Machinery To Enter the Nucleus, J. Virol, vol.88, pp.4132-4144, 2014.

H. Nishimura, T. Honjo, and N. Minato, Facilitation of ? Selection and Modification of Positive Selection in the Thymus of Pd-1-Deficient Mice, J. Exp. Med, vol.191, pp.891-898, 2000.

M. Nonnenmacher and T. Weber, Adeno-Associated Virus 2 Infection Requires Endocytosis through the CLIC/GEEC Pathway, Cell Host Microbe, vol.10, pp.563-576, 2011.

A. Nowrouzi, M. Penaud-budloo, C. Kaeppel, U. Appelt, C. Le-guiner et al., Integration Frequency and Intermolecular Recombination of rAAV Vectors in Non-human Primate Skeletal Muscle and Liver, Mol. Ther, vol.20, pp.1177-1186, 2012.

P. Ogston, K. Raj, and P. Beard, Productive Replication of Adeno-Associated Virus Can Occur in Human Papillomavirus Type 16 (HPV-16) Episome-Containing Keratinocytes and Is Augmented by the HPV-16 E2, Protein. J. Virol, vol.74, pp.3494-3504, 2000.

M. Oishi, F. Nagatsugi, S. Sasaki, Y. Nagasaki, and K. Kataoka, Smart polyion complex micelles for targeted intracellular delivery of PEGylated antisense oligonucleotides containing acid-labile linkages. Chembiochem Eur, J. Chem. Biol, vol.6, pp.718-725, 2005.

Y. Onishi, Z. Fehervari, T. Yamaguchi, and S. Sakaguchi, Foxp3+ natural regulatory T cells preferentially form aggregates on dendritic cells in vitro and actively inhibit their maturation, Proc. Natl. Acad. Sci. U. S. A, vol.105, pp.10113-10118, 2008.

E. Ozkaynak, L. Wang, A. Goodearl, K. Mcdonald, S. Qin et al., Programmed death-1 targeting can promote allograft survival, J. Immunol. Baltim. Md, vol.169, pp.6546-6553, 1950.

I. A. Parish, S. Rao, G. K. Smyth, T. Juelich, G. S. Denyer et al., The molecular signature of CD8+ T cells undergoing deletional tolerance, Blood, vol.113, pp.4575-4585, 2009.

K. Park, J. Lee, J. Park, J. Joh, C. H. Kwon et al., Adeno-Associated Virus 2-Mediated Hepatocellular Carcinoma is Very Rare in Korean Patients, Ann. Lab. Med, vol.36, pp.469-474, 2016.

A. M. Paterson, S. B. Lovitch, P. T. Sage, V. R. Juneja, Y. Lee et al., Deletion of CTLA-4 on regulatory T cells during adulthood leads to resistance to autoimmunity, J. Exp. Med, vol.212, pp.1603-1621, 2015.

C. Pedros, A. J. Canonigo-balancio, K. Kong, and A. Altman, Requirement of Treg-intrinsic CTLA4/PKC? signaling pathway for suppressing tumor immunity, JCI Insight, vol.2

D. Perez-witzke, M. A. Miranda-garcía, N. Suárez, R. Becerra, K. Duque et al., CTLA4Fc?, a novel soluble fusion protein that binds B7 molecules and the IgE receptors, and reduces human in vitro soluble CD23 production and lymphocyte proliferation, Immunology, vol.148, pp.40-55, 2016.

S. Pillay, N. L. Meyer, A. .. Puschnik, O. Davulcu, J. Diep et al., An essential receptor for adeno-associated virus infection, Nature, vol.530, pp.108-112, 2016.

M. Poon, W. Tsang, S. Chan, H. Li, H. Ng et al., DyslexiaAssociated Kiaa0319-Like Protein Interacts with Axon Guidance Receptor Nogo Receptor 1, Cell. Mol. Neurobiol, vol.31, pp.27-35, 2011.

M. Pyzik and C. A. Piccirillo, TGF-beta1 modulates Foxp3 expression and regulatory activity in distinct CD4+ T cell subsets, J. Leukoc. Biol, vol.82, pp.335-346, 2007.

D. Quandt, H. Hoff, M. Rudolph, S. Fillatreau, and M. C. Brunner-weinzierl, A New Role of CTLA-4 on B Cells in Thymus-Dependent Immune Responses In Vivo, J. Immunol, vol.179, pp.7316-7324, 2007.

O. S. Qureshi, Y. Zheng, K. Nakamura, K. Attridge, C. Manzotti et al., Trans-endocytosis of CD80 and CD86: a molecular basis for the cell extrinsic function of CTLA-4, Science, vol.332, pp.600-603, 2011.

J. E. Rabinowitz and R. J. Samulski, Building a Better Vector: The Manipulation of AAV Virions, Virology, vol.278, pp.301-308, 2000.

S. E. Raper, N. Chirmule, F. S. Lee, N. A. Wivel, A. Bagg et al., , 2003.

, Fatal systemic inflammatory response syndrome in a ornithine transcarbamylase deficient patient following adenoviral gene transfer, Mol. Genet. Metab, vol.80, pp.148-158

M. Razmara, B. Hilliard, A. K. Ziarani, Y. H. Chen, and M. L. Tykocinski, CTLA-4·Ig converts naive CD4+CD25? T cells into CD4+CD25+ regulatory T cells, Int. Immunol, vol.20, pp.471-483, 2008.

G. L. Rogers, A. T. Martino, G. V. Aslanidi, G. R. Jayandharan, A. Srivastava et al., Innate Immune Responses to AAV Vectors, Front. Microbiol, vol.2, 2011.

G. L. Rogers, M. Suzuki, I. Zolotukhin, D. M. Markusic, L. M. Morel et al., Unique Roles of TLR9-and MyD88-Dependent and -Independent Pathways in Adaptive Immune Responses to AAV-Mediated Gene Transfer, J. Innate Immun, vol.7, pp.302-314, 2015.

M. R. Rollins, G. Johnson, and R. M. , CD80 Expressed by CD8+ T Cells Contributes to PD-L1-Induced Apoptosis of Activated CD8+ T Cells, J. Immunol. Res, 2017.

M. G. Roncarolo, S. Gregori, M. Battaglia, R. Bacchetta, K. Fleischhauer et al., Interleukin-10-secreting type 1 regulatory T cells in rodents and humans, Immunol. Rev, vol.212, pp.28-50, 2006.

C. A. Sabatos, S. Chakravarti, E. Cha, A. Schubart, A. Sánchez-fueyo et al., Interaction of Tim-3 and Tim-3 ligand regulates T helper type 1 responses and induction of peripheral tolerance, Nat. Immunol, vol.4, pp.1102-1110, 2003.

T. T. Sakaguchi and S. , Naturally Arising CD25+CD4+ Regulatory T Cells in Maintaining Immunologic Self-Tolerance and Preventing Autoimmune Disease, 2003.

S. Sakaguchi, T. Yamaguchi, T. Nomura, and M. Ono, Regulatory T Cells and Immune Tolerance, Cell, vol.133, pp.775-787, 2008.

J. L. Santiago-ortiz and D. V. Schaffer, Adeno-associated virus (AAV) vectors in cancer gene therapy, J. Control. Release Off. J. Control. Release Soc, vol.240, pp.287-301, 2016.

J. R. Schlehofer, M. Ehrbar, and H. Zur-hausen, Vaccinia virus, herpes simplex virus, and carcinogens induce DNA amplification in a human cell line and support replication of a helpervirus dependent parvovirus, Virology, vol.152, pp.110-117, 1986.

J. E. Schmitz, M. J. Kuroda, S. Santra, V. G. Sasseville, M. A. Simon et al., Control of viremia in simian immunodeficiency virus infection by CD8+ lymphocytes, Science, vol.283, pp.857-860, 1999.

H. Schneider, C. , and C. , In utero gene therapy: The case for, 1999.

H. Schneider, J. Downey, A. Smith, B. H. Zinselmeyer, C. Rush et al., Reversal of the TCR stop signal by CTLA-4, Science, vol.313, pp.1972-1975, 2006.

B. C. Schnepp, K. R. Clark, D. L. Klemanski, C. A. Pacak, J. et al., Genetic Fate of Recombinant Adeno-Associated Virus Vector Genomes in Muscle, J. Virol, vol.77, pp.3495-3504, 2003.

B. C. Schnepp, R. L. Jensen, K. R. Clark, J. , and P. R. , Infectious Molecular Clones of AdenoAssociated Virus Isolated Directly from Human Tissues, J. Virol, vol.83, pp.1456-1464, 2009.

C. Sciorati, E. Rigamonti, A. A. Manfredi, and P. Rovere-querini, Cell death, clearance and immunity in the skeletal muscle, Cell Death Differ, vol.23, pp.927-937, 2016.

R. Selot, S. Arumugam, B. Mary, S. Cheemadan, and G. R. Jayandharan, , 2017.

, Vectors That Partially Evade Neutralizing Antibodies during Hepatic Gene Transfer, Front. Pharmacol, vol.8

F. Shen, R. Kuo, M. Milon-camus, Z. Han, L. Jiang et al., Intravenous delivery of AAV9 vector mediates effective gene expression in ischemic stroke lesion and brain angiogenic foci, Stroke J. Cereb. Circ, vol.44, pp.252-254, 2013.

P. I. Sidiropoulos and D. T. Boumpas, Lessons learned from anti-CD40L treatment in systemic lupus erythematosus patients, Lupus, vol.13, pp.391-397, 2004.

J. H. Sim, M. J. Park, S. Park, and E. Lee, Altered expression of costimulatory molecules in Behçet's disease according to clinical activity, Br. J. Dermatol, vol.164, pp.1285-1291, 2011.

K. Siva, G. Covello, and M. A. Denti, Exon-Skipping Antisense Oligonucleotides to Correct Missplicing in Neurogenetic Diseases, Nucleic Acid Ther, vol.24, pp.69-86, 2014.

A. J. Smith, F. C. Schlichtenbrede, M. Tschernutter, J. W. Bainbridge, A. J. Thrasher et al., , 2003.

, AAV-Mediated gene transfer slows photoreceptor loss in the RCS rat model of retinitis pigmentosa, Mol. Ther, vol.8, pp.188-195

R. O. Snyder, Adeno-associated virus-mediated gene delivery, J. Gene Med, vol.1, pp.166-175, 1999.

R. O. Snyder, C. H. Miao, G. A. Patijn, S. K. Spratt, O. Danos et al., Persistent and therapeutic concentrations of human factor IX in mice after hepatic gene transfer of recombinant AAV vectors, Nat. Genet, vol.16, pp.270-276, 1997.

M. Song, D. Chen, B. Lu, C. Wang, J. Zhang et al.,

, PTEN Loss Increases PD-L1 Protein Expression and Affects the Correlation between PD-L1 Expression and Clinical Parameters in Colorectal Cancer, PLoS ONE, vol.8

M. Song, C. Hong, S. J. Park, J. Kim, B. Yang et al., Protective effects of Fc-fused PD-L1 on two different animal models of colitis, Gut, vol.64, pp.260-271, 2015.

E. Sonkoly, P. Janson, M. Majuri, T. Savinko, N. Fyhrquist et al., MiR-155 is overexpressed in patients with atopic dermatitis and modulates Tcell proliferative responses by targeting cytotoxic T lymphocyte-associated antigen 4, J. Allergy Clin. Immunol, vol.126, pp.581-589, 2010.

G. Stallone, B. Infante, A. Di-lorenzo, F. Rascio, G. Zaza et al., mTOR inhibitors effects on regulatory T cells and on dendritic cells, J. Transl. Med, vol.14, 2016.

S. K. Subudhi, P. Zhou, L. M. Yerian, R. K. Chin, J. C. Lo et al., Local expression of B7-H1 promotes organ-specific autoimmunity and transplant rejection, 2004.

C. Summerford and R. J. Samulski, AAVR: A Multi-Serotype Receptor for AAV, Mol. Ther, vol.24, pp.663-666, 2016.

X. Tai, M. Cowan, L. Feigenbaum, and A. Singer, CD28 costimulation of developing thymocytes induces Foxp3 expression and regulatory T cell differentiation independently of interleukin 2, Nat. Immunol, vol.6, pp.152-162, 2005.

Q. Tang, E. K. Boden, K. J. Henriksen, H. Bour-jordan, M. Bi et al., Distinct roles of CTLA-4 and TGF-beta in CD4+CD25+ regulatory T cell function, Eur. J. Immunol, vol.34, pp.2996-3005, 2004.

Y. Tang, J. Cummins, J. Huard, W. , and B. , AAV-directed muscular dystrophy gene therapy, Expert Opin. Biol. Ther, vol.10, pp.395-408, 2010.

A. W. Thomson and P. A. Knolle, Antigen-presenting cell function in the tolerogenic liver environment, Nat. Rev. Immunol, vol.10, pp.753-766, 2010.

A. M. Thornton and E. M. Shevach, CD4+CD25+ Immunoregulatory T Cells Suppress Polyclonal T Cell Activation In Vitro by Inhibiting Interleukin 2 Production, J. Exp. Med, vol.188, pp.287-296, 1998.

E. A. Tivol, F. Borriello, A. N. Schweitzer, W. P. Lynch, J. A. Bluestone et al., Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4, Immunity, vol.3, pp.541-547, 1995.

E. A. Tivol, S. D. Boyd, S. Mckeon, F. Borriello, P. Nickerson et al., , 1997.

, CTLA4Ig prevents lymphoproliferation and fatal multiorgan tissue destruction in CTLA-4-deficient mice, J. Immunol. Baltim. Md, vol.158, pp.5091-5094, 1950.

Y. Tseng, B. L. Gurda, P. Chipman, R. Mckenna, S. Afione et al., Adeno-Associated Virus Serotype 1 (AAV1)-and AAV5-Antibody Complex Structures Reveal Evolutionary Commonalities in Parvovirus Antigenic Reactivity, J. Virol, vol.89, pp.1794-1808, 2014.

Y. Tsutsumi, X. Jie, K. Ihara, A. Nomura, S. Kanemitsu et al., Phenotypic and genetic analyses of T-cell-mediated immunoregulation in patients with Type 1 diabetes, Diabet. Med. J. Br. Diabet. Assoc, vol.23, pp.1145-1150, 2006.

M. E. Turnis, D. V. Sawant, A. L. Szymczak-workman, L. P. Andrews, G. M. Delgoffe et al., Interleukin-35 limits anti-tumor immunity, Immunity, vol.44, pp.316-329, 2016.

V. M. Velazquez, D. G. Bowen, and C. M. Walker, Silencing of T lymphocytes by antigen-driven programmed death in recombinant adeno-associated virus vector-mediated gene therapy, Blood, vol.113, pp.538-545, 2009.

D. A. Vignali, L. W. Collison, and C. J. Workman, How regulatory T cells work, Nat. Rev. Immunol, vol.8, pp.523-532, 2008.

T. L. Walunas, D. J. Lenschow, C. Y. Bakker, P. S. Linsley, G. J. Freeman et al., CTLA-4 can function as a negative regulator of T cell activation, Immunity, vol.1, pp.405-413, 1994.

B. Wan, H. Nie, A. Liu, G. Feng, D. He et al., Aberrant Regulation of Synovial T Cell Activation by Soluble Costimulatory Molecules in Rheumatoid Arthritis, J. Immunol, vol.177, pp.8844-8850, 2006.

L. Wang, E. Dobrzynski, A. Schlachterman, O. Cao, and R. W. Herzog, Systemic protein delivery by muscle-gene transfer is limited by a local immune response, Blood, vol.105, pp.4226-4234, 2005.

L. Wang, Z. Li, X. Hu, K. P. Muyayalo, Y. Zhang et al., The roles of the PD, 2017.

, PD-L1 pathway at immunologically privileged sites, Am. J. Reprod. Immunol. N. Y, p.78, 1989.

P. Waterhouse, J. M. Penninger, E. Timms, A. Wakeham, A. Shahinian et al., Lymphoproliferative Disorders with Early Lethality in Mice Deficient in Ctla-4, Science, vol.270, pp.985-988, 1995.

M. Wawrzyniak, L. O'mahony, A. , and M. , Role of Regulatory Cells in Oral Tolerance, Allergy Asthma Immunol. Res, vol.9, pp.107-115, 2017.

J. A. Williams, J. Zhang, H. Jeon, T. Nitta, I. Ohigashi et al., Thymic medullary epithelium and thymocyte self tolerance require cooperation between CD28-CD80/86 and CD40-CD40L costimulatory pathways, J. Immunol. Baltim. Md, pp.630-640, 2014.

K. Wing, Y. Onishi, P. Prieto-martin, T. Yamaguchi, M. Miyara et al., CTLA-4 Control over Foxp3+ Regulatory T Cell Function, Science, vol.322, pp.271-275, 2008.

W. Xiao, K. H. Warrington, P. Hearing, J. Hughes, and N. Muzyczka, Adenovirus-Facilitated Nuclear Translocation of Adeno-Associated Virus Type 2, J. Virol, vol.76, pp.11505-11517, 2002.

H. Yagi, T. Nomura, K. Nakamura, S. Yamazaki, T. Kitawaki et al., Crucial role of FOXP3 in the development and function of human CD25+CD4+ regulatory T cells, Int. Immunol, vol.16, pp.1643-1656, 2004.

T. Yamazaki, H. Akiba, H. Iwai, H. Matsuda, M. Aoki et al., Expression of Programmed Death 1 Ligands by Murine T Cells and APC, J. Immunol, vol.169, pp.5538-5545, 2002.

Z. Yan, R. Zak, Y. Zhang, and J. F. Engelhardt, Inverted Terminal Repeat Sequences Are Important for Intermolecular Recombination and Circularization of Adeno-Associated Virus Genomes, J. Virol, vol.79, pp.364-379, 2005.

X. Yu, K. Harden, L. C. Gonzalez, M. Francesco, E. Chiang et al., The surface protein TIGIT suppresses T cell activation by promoting the generation of mature immunoregulatory dendritic cells, Nat. Immunol, vol.10, pp.48-57, 2009.

A. Zaiss, Q. Liu, G. P. Bowen, N. C. Wong, J. S. Bartlett et al., Differential activation of innate immune responses by adenovirus and adeno-associated virus vectors, J. Virol, vol.76, pp.4580-4590, 2002.

P. E. Zarek, C. Huang, E. R. Lutz, J. Kowalski, M. R. Horton et al., A2A receptor signaling promotes peripheral tolerance by inducing T-cell anergy and the generation of adaptive regulatory T cells, Blood, vol.111, pp.251-259, 2008.

H. Zhang, R. Watanabe, G. J. Berry, A. Vaglio, Y. J. Liao et al., Immunoinhibitory checkpoint deficiency in medium and large vessel vasculitis, Proc. Natl. Acad. Sci, 2017.

J. Zhang, M. Ding, K. Xu, L. Mao, and J. Zheng, shRNA-armed conditionally replicative adenoviruses: a promising approach for cancer therapy, Oncotarget, vol.7, pp.29824-29834, 2016.

Y. Zhang, J. Maksimovic, G. Naselli, J. Qian, M. Chopin et al.,

, Genome-wide DNA methylation analysis identifies hypomethylated genes regulated by FOXP3 in human regulatory T cells, Blood, vol.122, pp.2823-2836

Y. Zhao, D. L. Harrison, Y. Song, J. Ji, J. Huang et al., Antigen-Presenting Cell-Intrinsic PD-1 Neutralizes PD-L1 in cis to Attenuate PD-1 Signaling in T Cells, Cell Rep, vol.24, pp.379-390, 2018.

S. G. Zheng, J. H. Wang, W. Stohl, K. S. Kim, J. D. Gray et al., TGF-beta requires CTLA-4 early after T cell activation to induce FoxP3 and generate adaptive CD4+CD25+ regulatory cells, J. Immunol. Baltim. Md, vol.176, pp.3321-3329, 1950.

H. Zhou, L. Xiong, Y. Wang, L. Ding, S. Hu et al., Treatment of murine lupus with PD-LIg, Clin. Immunol. Orlando Fla, vol.162, pp.1-8, 2016.

C. Zhu, A. C. Anderson, A. Schubart, H. Xiong, J. Imitola et al., The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity, Nat. Immunol, vol.6, pp.1245-1252, 2005.

J. Zhu, X. Huang, Y. , and Y. , The TLR9-MyD88 pathway is critical for adaptive immune responses to adeno-associated virus gene therapy vectors in mice, J. Clin. Invest, vol.119, pp.2388-2398, 2009.

C. Zincarelli, S. Soltys, G. Rengo, and J. E. Rabinowitz, Analysis of AAV Serotypes 1-9 Mediated Gene Expression and Tropism in Mice After Systemic Injection, Mol. Ther, vol.16, pp.1073-1080, 2008.