Dendritic cells crossprime allo-specific self-restricted CD4(+) T cells after coculture with dead allogeneic cells

Indirect alloreactivity, i.e., the recognition of allopeptides on self-MHC molecules, contributes both to acute and chronic rejection of transplants. The antigen presenting cell priming these allo-specific self-restricted T cells is unknown. We demontrate that dendritic cells, which have been matured in the presence of necrotic allogeneic cells, can crossprime allo-specific self-restricted CD4(+) T cells in vitro. We demonstrate dendrtitic cell mediated crosspriming of HLA-DR13 specific, HLA-DR7 restricted and HLA-DR1 specific, HLA-DR11 restricted CD4(+) T cells. The allo-specific self-restricted CD4(+) T cells primed in our culture system secrete predominantly Th1 and not Th2 cytokines. The use of dendritic cells to monitor the indirect pathway of alloreactivity should help to design and understand interventions against acute and chronic transplant rejection.