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.