@article {542431,
	title = {PD-1 regulates self-reactive CD8+ T cell responses to antigen in lymph nodes and tissues.},
	journal = {J Immunol},
	volume = {179},
	number = {8},
	year = {2007},
	month = {2007 Oct 15},
	pages = {5064-70},
	abstract = {PD-1, an inhibitory receptor expressed on activated lymphocytes, regulates tolerance and autoimmunity. We tested the role of PD-1:PD-1 ligand (PD-L) interactions in cross-presentation and the generation and control of CD8(+) responses against self-Ag. Ag-naive PD-1(-/-) OVA-specific OT-I CD8(+) T cells exhibited exacerbated responses to cross-presented Ag in mice expressing soluble OVA under the control of the rat insulin promoter (RIP-ova(high)). Following adoptive transfer into RIP-ova(high) recipients, PD-1(-/-) OT-I T cells expanded in the pancreatic lymph node. In contrast to wild-type OT-I cells, PD-1(-/-) OT-I T cells secreted IFN-gamma and migrated into the pancreas, ultimately causing diabetes. Loss of PD-1 affected CD8(+) cells intrinsically, and did not significantly alter the responses of wild-type OT-I T cells adoptively transferred into the same RIP-ova(high) recipient mouse. PD-1:PD-L interactions also limited CD8(+) effector cells, and PD-L1 expression on parenchymal tissues protected against effector OT-I T cell attack. Finally, we found that the loss of PD-1 on effector OT-I cells lowers the threshold for Ag recognition in peripheral tissues. These findings indicate two checkpoints where PD-1 attenuates self-reactive T cell responses: presentation of self-Ag to naive self-reactive T cells by dendritic cells in the draining lymph node and reactivation of pathogenic self-reactive T cells in the target organ.},
	keywords = {Animals, Antigens, Antigens, CD274, Antigens, CD80, Antigens, Surface, Apoptosis Regulatory Proteins, CD8-Positive T-Lymphocytes, Cell Line, Cross-Priming, Lymph Nodes, Lymphocyte Activation, Membrane Glycoproteins, Mice, Mice, Inbred C57BL, Mice, Knockout, Ovalbumin, Pancreas, Peptides, Programmed Cell Death 1 Receptor, Self Tolerance},
	issn = {0022-1767},
	author = {Keir, Mary E and Freeman, Gordon J and Sharpe, Arlene H}
}
