Anti-Programmed Cell Death 1 Antibody Reduces CD4(+)PD-1(+) T Cells and Relieves the Lupus-Like Nephritis of NZB/W F1 Mice

作者：Kasagi Shimpei; Kawano Seiji; Okazaki Taku; Honjo Tasuku; Morinobu Akio; Hatachi Saori; Shimatani Kenichiro; Tanaka Yoshimasa; Minato Nagahiro; Kumagai Shunichi^*

来源：The Journal of Immunology, 2010, 184(5): 2337-2347.

DOI：10.4049/jimmunol.0901652

Programmed cell death 1 (PD-1) is an immunosuppressive receptor that transduces an inhibitory signal into activated T cells. Although a single nucleotide polymorphism in the gene for PD-1 is associated with susceptibility to systemic lupus erythematosus, the role of PD-1 in systemic lupus erythematosus is still not well understood. In this study, we used NZB/W F1 mice, a model of lupus-like nephritis, to examine the function of PD-1 and its ligands. PD-1 was predominantly expressed on CD4(+) T cells that infiltrated the kidney, and CD4(+)PD-1(high) T cells produced higher levels of IFN-gamma than CD4(+)PD-1(low) or CD4(+)PD-1(-) T cells. Stimulation with PMA/ionomycin caused splenic CD4(+)PD-1(+) T cells to secrete high levels of IFN-gamma, IL-10, low levels of TNF-alpha, faint levels of IL-2, IL-21, and no IL-4, IL-17. In vivo anti-PD-1 mAb treatment reduced the number of CD4(+)PD-1(+) T cells in the kidney of NZB/W F1 mice and significantly reduced their mortality rate (p = 0.03). Conversely, blocking PD-L1 using an anti-PD-L1 mAb increased the number of CD4(+)PD-1(+) T cells in the kidney, enhanced serum IFN-gamma, IL-10, and IgG2a ds-DNA-Ab levels, accelerated the nephritis, and increased the mortality rate. We conclude that CD4(+)PD-1(high) T cells are dysregulated IFN-gamma-producing, proinflammatory cells in NZB/W F1 mice. The Journal of Immunology, 2010, 184: 2337-2347.

• 出版日期2010-3-1