Type 1 regulatory T cells specific for collagen type II as an efficient cell-based therapy in arthritis

Hélène Asnagli (1) , Delphine Martire (2) , Nathalie Belmonte (3) , Julie Quentin (2) , Hervé Bastian , Mathilde Boucard-Jourdin , Papa Babacar Fall , Anne-Laure Mausset-Bonnefont (2) , Amélie Mantello-Moreau , Sandrine Rouquier , Irène Marchetti , Christian Jorgensen (4) , Arnaud Foussat (1) , Pascale Louis-Plence (2)

1 TxCell
2 Cellules souches mésenchymateuses, environnement articulaire et immunothérapies de la polyarthrite rhumatoide
3 IBDC - Institut de signalisation, biologie du développement et cancer - Institute of Developmental Biology and Cancer
4 Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB)

Introduction: Regulatory T (Treg) cells play a crucial role in preventing autoimmune diseases and are an ideal target for the development of therapies designed to suppress inflammation in an antigen-specific manner. Type 1 regulatory T (Tr1) cells are defined by their capacity to produce high levels of interleukin 10 (IL-10), which contributes to their ability to suppress pathological immune responses in several settings. The aim of this study was to evaluate the therapeutic potential of collagen type II–specific Tr1 (Col-Treg) cells in two models of rheumatoid arthritis (RA) in mice. Methods: Col-Treg clones were isolated and expanded from collagen-specific TCR transgenic mice. Their cytokine secretion profile and phenotype characterization were studied. The therapeutic potential of Col-Treg cells was evaluated after adoptive transfer in collagen-antibody– and collagen-induced arthritis models. The in vivo suppressive mechanism of Col-Treg clones on effector T-cell proliferation was also investigated. Results: Col-Treg clones are characterized by their specific cytokine profile (IL-10highIL-4negIFN-γint) and mediate contact-independent immune suppression. They also share with natural Tregs high expression of GITR, CD39 and granzyme B. A single infusion of Col-Treg cells reduced the incidence and clinical symptoms of arthritis in both preventive and curative settings, with a significant impact on collagen type II antibodies. Importantly, injection of antigen-specific Tr1 cells decreased the proliferation of antigen-specific effector T cells in vivo significantly. Conclusions: Our results demonstrate the therapeutic potential of Col-Treg cells in two models of RA, providing evidence that Col-Treg could be an efficient cell-based therapy for RA patients whose disease is refractory to current treatments.

Domaines: Immunologie

Hélène Asnagli, Delphine Martire, Nathalie Belmonte, Julie Quentin, Hervé Bastian, et al.. Type 1 regulatory T cells specific for collagen type II as an efficient cell-based therapy in arthritis. Arthritis Research and Therapy, 2014, 16 (3), ⟨10.1186/ar4567⟩. ⟨hal-02397296⟩