Cutting Edge: Programmed death (PD) ligand-1/PD-1 interaction is required for CD8+ T cell tolerance to tissue antigens.
Constitutive presentation of tissue Ags by dendritic cells results in tolerance of autoreactive CD8+ T cells; however, the underlying molecular mechanisms are not well understood. In this study we show that programmed death (PD)-1, an inhibitory receptor of the CD28 family, is required for tolerance induction of autoreactive CD8+ T cells. An antagonistic Ab against PD-1 provoked destructive autoimmune diabetes in RIP-mOVA mice expressing chicken OVA in the pancreatic islet cells, which received naive OVA-specific CD8+ OT-I cells. This effect was mediated by the PD ligand (PD-L) PD-L1 but not by PD-L2. An increased number of effector OT-I cells recovered from the pancreatic lymph nodes of anti-PD-L1-treated mice showed down-regulation of PD-1. Furthermore, the blockade of PD-1/PD-L1 interaction during the priming phase did not significantly affect OT-I cell division but enhanced its granzyme B, IFN-gamma, and IL-2 production. Thus, during the presentation of tissue Ags to CD8+ T cells, PD-1/PD-L1 interaction crucially controls the effector differentiation of autoreactive T cells to maintain self-tolerance.
Martin-Orozco
Natalia
N
University of Texas M.D. Anderson Cancer Center, 7455 Fannin, Houston, TX 77030, USA.
Wang
Yi-Hong
YH
Yagita
Hideo
H
Dong
Chen
C
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000943:Antigens, Differentiation / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D018122:B7-1 Antigen / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D060890:B7-H1 Antigen; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002645:Chickens; D003713:Dendritic Cells; D003921:Diabetes Mellitus, Experimental / Q000276:immunology; D050417:Insulin-Secreting Cells / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D010455:Peptides / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D061026:Programmed Cell Death 1 Receptor; D017634:Self Tolerance / Q000276:immunology*
D000943:Antigens, Differentiation; D051017:Apoptosis Regulatory Proteins; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse; D008562:Membrane Glycoproteins; C491383:Pdcd1 protein, mouse; D010455:Peptides; D061026:Programmed Cell Death 1 Receptor; D010047:Ovalbumin