Non-classical pathways of cell-mediated allograft rejection: new challenges for tolerance induction?

Allograft rejection results from separate pathways primarily controlled by CD4+ T cells. Refinement of transplantation models together with investigations on rejection occurring despite co-stimulation blockade revealed unexpected pathways involving CD8+ T cells, NK cells and Th2 cytokines. In this minireview, we discuss these non-classical pathways of allograft rejection and their relevance for the induction of tolerance in the clinics.