Abstract
We investigated the in vivo function of the B7 family member B7-H3 (also known as B7RP-2) by gene targeting. B7-H3 inhibited T cell proliferation mediated by antibody to T cell receptor or allogeneic antigen-presenting cells. B7-H3-deficient mice developed more severe airway inflammation than did wild-type mice in conditions in which T helper cells differentiated toward type 1 (TH1) rather than type 2 (TH2). B7-H3 expression was consistently enhanced by interferon-γ but suppressed by interleukin 4 in dendritic cells. B7-H3-deficient mice developed experimental autoimmune encephalomyelitis several days earlier than their wild-type littermates, and accumulated higher concentrations of autoantibodies to DNA. Thus, B7-H3 is a negative regulator that preferentially affects TH1 responses.
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Acknowledgements
We thank A. Tafuri and A. Shahinian for their preliminary data; T. Walker and S. Goncharova for technical assistance with airway inflammation experiments; A. Ho for help with EAE experiments; Z. Hao for advice on autoantibody analysis; D. Bouchard for cell sorting and preparation of the manuscript; and M. Saunders for scientific editing. This work was supported by the Canadian Network for Vaccines and Immunotherapeutics of Cancer and Chronic Viral Diseases. W.-K.S. is the recipient of a postdoctoral fellowship from the Cancer Research Institute.
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Suh, WK., Gajewska, B., Okada, H. et al. The B7 family member B7-H3 preferentially down-regulates T helper type 1–mediated immune responses. Nat Immunol 4, 899–906 (2003). https://doi.org/10.1038/ni967
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DOI: https://doi.org/10.1038/ni967
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