PD-1/PD-L1 Interaction Maintains Allogeneic Immune Tolerance Induced by Administration of Ultraviolet B-Irradiated Immature Dendritic Cells

Our previous study demonstrated that transfusion of ultraviolet b-irradiated immature dendritic cells (uvb-idcs) induced alloantigen-specific tolerance between two different strains of mice. programmed death-1 (pd-1) and programmed death ligand-1 (pd-l1) have been suggested to play an important role in maintaining immune tolerance. in the present study,we seek to address whether pd-1/pd-l1 plays a role in the maintenance of uvb-idc-induced tolerance. we first observe that the uvb-idc-induced alloantigen-specific tolerance can be maintained for over 6 weeks. supporting this,at 6 weeks after tolerance induction completion,alloantigen-specific tolerance is still able to be transferred to syngeneic naïve mice through adoptive transfer of cd4+ t cells. furthermore,skin transplantation study shows that the survival of allogeneic grafts is prolonged in those tolerant recipients. further studies show that pd-1/pd-l1 interaction is essential for maintaining the induced tolerance as blockade of pd-1/pd-l1 by anti-pd-l1 antibodies largely breaks the tolerance at both cellular and humoral immunological levels. importantly,we show that pd-1/pd-l1 interaction in tolerant mice is also essential for controlling alloantigen-responding t cells,which have never experienced alloantigens. the above findings suggest that pd-1/pd-l1 plays a crucial role in maintaining immune tolerance induced by uvb-idcs,as well as in actively controlling effector t cells specific to alloantigens. © 2016 lanfang zhang and chang-qing xia.