Blockade of B7-H1 on Macrophages Suppresses CD4+ T Cell Proliferation by Augmenting IFN-γ-Induced Nitric Oxide Production

Journal of Immunology - Tập 175 Số 3 - Trang 1586-1592 - 2005
Taiga Yamazaki1,2, Hisaya Akiba1,2, Akemi Koyanagi1,2, Miyuki Azuma1,2, Hideo Yagita1,2, Ko Okumura1,2
1Department of Immunology and Division of Cell Biology, Juntendo University School of Medicine, Tokyo, Japan
2Department of Molecular Immunology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan

Tóm tắt

Abstract PD-1 is an immunoinhibitory receptor that belongs to the CD28/CTLA-4 family. B7-H1 (PD-L1) and B7-DC (PD-L2), which belong to the B7 family, have been identified as ligands for PD-1. Paradoxically, it has been reported that both B7-H1 and B7-DC costimulate or inhibit T cell proliferation and cytokine production. To determine the role of B7-H1 and B7-DC in T cell-APC interactions, we examined the contribution of B7-H1 and B7-DC to CD4+ T cell activation by B cells, dendritic cells, and macrophages using anti-B7-H1, anti-B7-DC, and anti-PD-1 blocking mAbs. Anti-B7-H1 mAb and its Fab markedly inhibited the proliferation of anti-CD3-stimulated naive CD4+ T cells, but enhanced IL-2 and IFN-γ production in the presence of macrophages. The inhibition of T cell proliferation by anti-B7-H1 mAb was abolished by neutralizing anti-IFN-γ mAb. Coculture of CD4+ T cells and macrophages from IFN-γ-deficient or wild-type mice showed that CD4+ T cell-derived IFN-γ was mainly responsible for the inhibition of CD4+ T cell proliferation. Anti-B7-H1 mAb induced IFN-γ-mediated production of NO by macrophages, and inducible NO synthase inhibitors abrogated the inhibition of CD4+ T cell proliferation by anti-B7-H1 mAb. These results indicated that the inhibition of T cell proliferation by anti-B7-H1 mAb was due to enhanced IFN-γ production, which augmented NO production by macrophages, suggesting a critical role for B7-H1 on macrophages in regulating IFN-γ production by naive CD4+ T cells and, hence, NO production by macrophages.

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Journal of Immunology

Tập 175 Số 3

1586-1592

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