Complement regulator CD46 temporally regulates cytokine production by conventional and unconventional T cells

Claudia Kemper (1) , John Cardone (1) , Gaelle Le Friec (1) , Pierre Vantourout (1) , Andrew Roberts (1) , Anja Fuchs (1) , Ian Jackson (1) , Tesha Suddason (1) , Graham Lord (1) , John Petterson Atkinson (1) , Andrew Cope (1) , Adrian C Hayday (1)

1 MRC Centre for Transplantation

This study reveals a novel form of immunoregulation: engagement on CD4 T cells of the complement regulator CD46 promotes T1 effector potential, but as interleukin-2 (IL-2) accumulates, "switches" cells toward a regulatory phenotype, attenuating IL-2 production via the transcriptional regulator ICER/CREM, and upregulating IL-10 following interaction of the CD46-tail with SPAKinase. Activated CD4 T cells produce CD46 ligands, and blocking CD46 inhibits IL-10 production. Furthermore, CD4 T cells in rheumatoid arthritis fail to switch, consequently producing excessive interferon-γ. Finally, γδ T cells, which rarely produce IL-10, express an alternative CD46-isoform and cannot switch. Nonetheless, T cell receptor γδ-CD46 co-engagement suppresses effector cytokine production, establishing that CD46 employs multiple mechanisms to regulate different T cell subsets during an immune response.

Mots clés: Complement; T cells; Tolerance; Autoimmunity

Claudia Kemper, John Cardone, Gaelle Le Friec, Pierre Vantourout, Andrew Roberts, et al.. Complement regulator CD46 temporally regulates cytokine production by conventional and unconventional T cells. Nature Immunology, 2010, ⟨10.1038/ni.1917⟩. ⟨hal-00564091⟩