Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement

The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.


Anti-PD-1 Antibody Reduces CD4PD-1 T Cells and Relieves the Lupus-Like Nephritis of NZB/W F1 Mice

Kasagi1,  Shimpei, Kawano2,  Seiji, Okazaki3,  Taku, Honjo4,  Tasuku, Morinobu2,  Akio, Hatachi5,  Saori, Shimatani4,  Kenichiro

Kobe University Graduate School of Medicine,, Kobe, Japan,
Kobe University Graduate School of Medicine, Kobe, Japan,
Institute for Genome Research, University of Tokushima, Tokushima, Japan,
Kyoto University Graduate School of Medicine, Kyoto, Japan,
Kitano Hospital, Osaka, Japan

Purpose:

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 (SLE), PD-1's role in SLE is still not well understood. we used NZB/W F1 mice, a model of lupus-like nephritis, to examine the function of PD-1 and its ligands.

Method:

Immunohistochemistry, Intracellular cytokine assay, Antibody treatment using anti-PD-1 and anti-PD-L1 mAb, and CDC assay.

Results:

PD-1 was predominantly expressed on CD4+ T cells that infiltrated the kidney, and CD4+PD-1high T cells produced higher levels of IFN-g than CD4+PD-1low or CD4+PD-1- T cells. Stimulation with PMA/ionomycin caused splenic CD4+PD-1+ T cells to secrete high levels of IFN-g and IL-10, low levels of TNFa, and no IL-2, IL-4, or 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-g, IL-10, and IgG2a ds-DNA-Ab levels, accelerated the nephritis, and increased the mortality rate.

Conclusion:

CD4+PD-1high T cells are dysregulated IFN-g-producing, proinflammatory cells in NZB/W F1 mice.

To cite this abstract, please use the following information:
Kasagi, Shimpei, Kawano, Seiji, Okazaki, Taku, Honjo, Tasuku, Morinobu, Akio, Hatachi, Saori, et al; Anti-PD-1 Antibody Reduces CD4PD-1 T Cells and Relieves the Lupus-Like Nephritis of NZB/W F1 Mice [abstract]. Arthritis Rheum 2009;60 Suppl 10 :2015
DOI: 10.1002/art.27087

Abstract Supplement

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