%0 Journal Article %J J Immunol %D 2011 %T The programmed death-1 ligand 1:B7-1 pathway restrains diabetogenic effector T cells in vivo. %A Paterson, Alison M %A Brown, Keturah E %A Keir, Mary E %A Vanguri, Vijay K %A Riella, Leonardo V %A Chandraker, Anil %A Sayegh, Mohamed H %A Blazar, Bruce R %A Freeman, Gordon J %A Sharpe, Arlene H %K Adoptive Transfer %K Animals %K Antibodies, Blocking %K Antigens, CD %K Antigens, CD274 %K Antigens, CD80 %K Apoptosis Regulatory Proteins %K Autoimmune Diseases %K CD4-Positive T-Lymphocytes %K CD8-Positive T-Lymphocytes %K Diabetes Mellitus, Type 1 %K Female %K Growth Inhibitors %K Ligands %K Membrane Glycoproteins %K Mice %K Mice, Inbred NOD %K Mice, SCID %K Mice, Transgenic %K Peptides %K Programmed Cell Death 1 Receptor %K Protein Binding %K Signal Transduction %X 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. %B J Immunol %V 187 %P 1097-105 %8 2011 Aug 1 %G eng %N 3 %1 http://www.ncbi.nlm.nih.gov/pubmed/21697456?dopt=Abstract %R 10.4049/jimmunol.1003496