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The B7 family member B7-H3 preferentially down-regulates T helper type 1–mediated immune responses

Nature Immunology volume 4, pages 899–906 (2003)Cite this article

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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Figure 1: Generation of B7-H3-deficient mice.
Figure 2: Negative regulation of T cell function by B7-H3.
Figure 3: Augmented TH1-mediated lung inflammation in B7-H3-deficient mice.
Figure 4: Regulation of B7-H3 expression by IFN-γ and IL-4 in dendritic cells.
Figure 5: Earlier onset of EAE in B7-H3-deficient mice.
Figure 6: Accumulation of autoantibodies in B7-H3-deficient mice over time.
Figure 7: Normal antiviral CTL responses in the absence of B7-H3.

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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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  1. Beata U Gajewska and Hitoshi Okada: These authors contributed equally to this work.

Authors and Affiliations

  1. Advanced Medical Discovery Institute, Ontario Cancer Institute, and Departments of Medical Biophysics and Immunology, University of Toronto, 620 University Avenue, Toronto, M5G 2C1, Ontario, Canada

    Woong-Kyung Suh, Hitoshi Okada, Gordon S Duncan, Suzanne Plyte, Andrew Elia, Andrew Wakeham, Annick Itie, Stephen Chung, Joan Da Costa, Sudha Arya, Mark R Bray & Tak W Mak

  2. Department of Pathology and Molecular Medicine, McMaster University, Hamilton, L8N 3Z5, Ontario, Canada

    Beata U Gajewska & Manel Jordana

  3. Department of Immunology, University of Toronto, Toronto, M5S 1A8, Ontario, Canada

    Matthew A Gronski, Edward M Bertram, Wojciech Dawicki, Jacob Bukczynski, Pamela S Ohashi & Tania H Watts

  4. Amgen, One Amgen Center Drive, Thousand Oaks, 91320-1789, California, USA

    Tom Horan, Pauline Campbell, Kevin Gaida & Steven K Yoshinaga

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Correspondence to Woong-Kyung Suh or Tak W Mak.

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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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