Dendritic cells use endocytic pathway for cross‐priming Qa‐1‐restricted CD8αα+ Treg

Abstract

Here, for the first time, we describe the mechanism by which Qa‐1‐restricted TCRαβ+CD8αα+ Tregs are primed. CD8αα+ Treg are a novel subset of naturally occurring suppressor lymphocytes that control activated Vβ8.2+ CD4+ T cells mediating experimental autoimmune encephalomyelitis in H‐2u mice. CD8αα+ Treg recognize a peptide determinant from the conserved region of the Vβ8.2 chain. Here we show that dendritic cells pulsed with apoptotic Vβ8.2+ CD4+ T cells can crosspresent TCR‐derived peptides to Treg in vitro. Apoptotic T cells do not induce DC maturation. Toll‐like receptor agonists augment the DC's ability to prime the Treg. Using specific inhibitors of antigen presentation, we demonstrate the involvement of endosomal and proteasomal processing in the formation of Qa‐1/peptide complexes. DCs that have captured apoptotic T cells can also prime CD8αα+ Treg in vivo and prevent autoimmune disease. Collectively, our data suggest during the exhaustion phase following a productive immune response, apoptotic T cells are engulfed by the DCs, and upon appropriate activation by innate signals DCs can crossprime CD8αα+ Treg to mediate immune suppression. Supported by grants from the NIH, MSNRC to VK.