Regulatory T cells suppression of antigen-specific CD8+ T cells in vivo is contact-dependent

Abstract

Abstract T Regulatory cells (Tregs) plays an important role in regulating immune mediated responses against self and foreign antigens by various known and unknown mechanisms. Recent studies have shown that antigen-specific iTreg suppress CD4+ effectors T cells in vitro and in vivo by depleting peptide-MHC-II complexes from the DC surface. These, results raise questions as to how Treg suppress CD8+ T effectors, particularly in vivo. To explore Treg mediated suppression of CD8+ T cells, we generated CD4+ iTregs from OT-II mice specific for Ova323–339 in association with I-Ab and determined their capacity to suppress CD8+ T cells from OT-I mice specific for Ova257–264 in association with H-2Kb. CD4+ OT-II iTreg suppressed the in vitro proliferation of OT-I T cells in the presence of Dendritic Cells (DCs) pulsed with both Ova323–339 and Ova257–264 or with DCs singly pulsed with each peptide. Surprisingly, the expansion of OT-I CD8+ T cells in vivo was not suppressed by OT-II iTreg when the two peptides were presented on separately pulsed DCs but was suppressed when both peptides were presented on the same DCs. These results strongly suggest that suppression of the expansion of CD8+ T cells in vivo requires close contact between Treg and responder CD8+ T cell on the surface of the same DC and raise the possibility that Treg may remove a large molecular complex from the DC surface by a process of trogocytosis.