@article {542211,
	title = {The programmed death-1 ligand 1:B7-1 pathway restrains diabetogenic effector T cells in vivo.},
	journal = {J Immunol},
	volume = {187},
	number = {3},
	year = {2011},
	month = {2011 Aug 1},
	pages = {1097-105},
	abstract = {Programmed death-1 ligand 1 (PD-L1) is a coinhibitory molecule that negatively regulates multiple tolerance checkpoints. In the NOD mouse model, PD-L1 regulates the development of diabetes. PD-L1 has two binding partners, programmed death-1 and B7-1, but the significance of the PD-L1:B7-1 interaction in regulating self-reactive T cell responses is not yet clear. To investigate this issue in NOD mice, we have compared the effects of two anti-PD-L1 Abs that have different blocking activities. Anti-PD-L1 mAb 10F.2H11 sterically and functionally blocks only PD-L1:B7-1 interactions, whereas anti-PD-L1 mAb 10F.9G2 blocks both PD-L1:B7-1 and PD-L1:programmed death-1 interactions. Both Abs had potent, yet distinct effects in accelerating diabetes in NOD mice: the single-blocker 10F.2H11 mAb was more effective at precipitating diabetes in older (13-wk-old) than in younger (6- to 7-wk-old) mice, whereas the dual-blocker 10F.9G2 mAb rapidly induced diabetes in NOD mice of both ages. Similarly, 10F.2H11 accelerated diabetes in recipients of T cells from diabetic, but not prediabetic mice, whereas 10F.9G2 was effective in both settings. Both anti-PD-L1 mAbs precipitated diabetes in adoptive transfer models of CD4(+) and CD8(+) T cell-driven diabetes. Taken together, these data demonstrate that the PD-L1:B7-1 pathway inhibits potentially pathogenic self-reactive effector CD4(+) and CD8(+) T cell responses in vivo, and suggest that the immunoinhibitory functions of this pathway may be particularly important during the later phases of diabetogenesis.},
	keywords = {Adoptive Transfer, Animals, Antibodies, Blocking, Antigens, CD, Antigens, CD274, Antigens, CD80, Apoptosis Regulatory Proteins, Autoimmune Diseases, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Diabetes Mellitus, Type 1, Female, Growth Inhibitors, Ligands, Membrane Glycoproteins, Mice, Mice, Inbred NOD, Mice, SCID, Mice, Transgenic, Peptides, Programmed Cell Death 1 Receptor, Protein Binding, Signal Transduction},
	issn = {1550-6606},
	doi = {10.4049/jimmunol.1003496},
	author = {Paterson, Alison M and Brown, Keturah E and Keir, Mary E and Vanguri, Vijay K and Riella, Leonardo V and Chandraker, Anil and Sayegh, Mohamed H and Blazar, Bruce R and Freeman, Gordon J and Sharpe, Arlene H}
}
