title: PD-1/PD-L1 Interaction Maintains Allogeneic Immune Tolerance Induced by Administration of Ultraviolet B-Irradiated Immature Dendritic Cells.
abstract: 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.
authors.affiliation: Department of Hematology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China; Department of Chemotherapy, Weihai Municipal Hospital, Weihai 264200, China.
authors.forename: Lanfang
authors.identifier: 0000-0003-3159-9004
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Hematology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China; Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL 32610, USA.
authors.forename: Chang-Qing
authors.identifier: 0000-0002-3832-1091
authors.initials: CQ
authors.lastname: Xia
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D060890:B7-H1 Antigen / Q000378:metabolism*; D006085:Graft Survival / Q000276:immunology; D007108:Immune Tolerance / Q000528:radiation effects; D007519:Isoantigens / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism*; D011485:Protein Binding; D016038:Skin Transplantation; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: D060890:B7-H1 Antigen; D007519:Isoantigens; D061026:Programmed Cell Death 1 Receptor