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 CD8alpha(+) or CD103(+) DCs, demonstrating the critical role of these cells in alloreactivity. Using D(b) -restricted anti-viral F5 transgenic TCR T cells, which we demonstrate are alloreactive with H-2K(d) , we show that cross-dressing of CD8alpha(+) and CD103(+) primes CD8(+) T cell or an 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.