PD-L1/PD-1 signal deficiency promotes allogeneic immune responses and accelerates heart allograft rejection.

Background: PD-L1, a ligand for programmed death 1 (PD-1), delivers a negative costimulatory signal to T cells and plays a critical role in the regulation of peripheral tolerance.

Methods: We used PD-L1(-/-) mice to evaluate the role of the PD-L1 signal on allogeneic immune responses in vivo and the underlying mechanisms. Heart transplantation was performed from PD-L1(-/-) donors or recipients in major histocompatibility complex fully mismatched mouse combinations.

Enhancement of NKT cells and increase in regulatory T cells results in improved allograft survival.

Background: Natural killer T (NKT) cells can serve as regulatory cells important in peripheral tolerance. In an experimental colitis model, it was shown that FK506 enhances the tolerizing effect of regulatory NKT cells induced by oral tolerance. We explored whether a subtherapeutic dose of FK506 could enhance the tolerizing effect of NKT cells induced by oral administration of donor spleen cells (SCs) in the pre-transplant period to prolong heart allograft survival.