@article {542491,
	title = {Tissue expression of PD-L1 mediates peripheral T cell tolerance.},
	journal = {J Exp Med},
	volume = {203},
	number = {4},
	year = {2006},
	month = {2006 Apr 17},
	pages = {883-95},
	abstract = {Programmed death 1 (PD-1), an inhibitory receptor expressed on activated lymphocytes, regulates tolerance and autoimmunity. PD-1 has two ligands: PD-1 ligand 1 (PD-L1), which is expressed broadly on hematopoietic and parenchymal cells, including pancreatic islet cells; and PD-L2, which is restricted to macrophages and dendritic cells. To investigate whether PD-L1 and PD-L2 have synergistic or unique roles in regulating T cell activation and tolerance, we generated mice lacking PD-L1 and PD-L2 (PD-L1/PD-L2(-/-) mice) and compared them to mice lacking either PD-L. PD-L1 and PD-L2 have overlapping functions in inhibiting interleukin-2 and interferon-gamma production during T cell activation. However, PD-L1 has a unique and critical role in controlling self-reactive T cells in the pancreas. Our studies with bone marrow chimeras demonstrate that PD-L1/PD-L2 expression only on antigen-presenting cells is insufficient to prevent the early onset diabetes that develops in PD-L1/PD-L2(-/-) non-obese diabetic mice. PD-L1 expression in islets protects against immunopathology after transplantation of syngeneic islets into diabetic recipients. PD-L1 inhibits pathogenic self-reactive CD4+ T cell-mediated tissue destruction and effector cytokine production. These data provide evidence that PD-L1 expression on parenchymal cells rather than hematopoietic cells protects against autoimmune diabetes and point to a novel role for PD-1-PD-L1 interactions in mediating tissue tolerance.},
	keywords = {Animals, Antigens, CD274, Antigens, CD80, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cells, Cultured, Cytokines, Diabetes Mellitus, Type 1, Hematopoietic Stem Cells, Immune Tolerance, Interferon-gamma, Membrane Glycoproteins, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Inbred NOD, Mice, Knockout, Mice, SCID, Organ Specificity, Peptides, Programmed Cell Death 1 Ligand 2 Protein, T-Lymphocytes},
	issn = {0022-1007},
	doi = {10.1084/jem.20051776},
	author = {Keir, Mary E and Liang, Spencer C and Guleria, Indira and Latchman, Yvette E and Qipo, Andi and Albacker, Lee A and Koulmanda, Maria and Freeman, Gordon J and Sayegh, Mohamed H and Sharpe, Arlene H}
}
