Host CD8α + and CD103 + dendritic cells prime transplant antigen‐specific CD8 + T cells via cross‐dressing

The participation of dendritic cells (DCs) in CD8 + T‐cell‐mediated allograft rejection is a long‐standing question of great clinical relevance for tissue transplantation. Here, we show that Batf3 −/− mice demonstrate delayed allo‐skin graft rejection and are deficient in priming allo‐specific CD8 + T cells. Batf3 −/− mouse priming is restored by transferring either purified CD8α + or CD103 + DCs, demonstrating the critical role of these cells in alloreactivity. Using D b ‐restricted antiviral F5 transgenic T‐cell receptor T cells, which we demonstrate are alloreactive with H‐2K d , we show that cross‐dressing of CD8α + and CD103 + primes CD8 + T‐cell or allo‐specific responses in vitro and in vivo . These findings suggest novel strategies for moderating tissue rejection based on interfering with DC cross‐dressing or subsequent interaction with T cells.