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B7-H3: A costimulatory molecule for T cell activation and IFN-γ production

Nature Immunology volume 2, pages 269–274 (2001)Cite this article

Abstract

We describe here a newly identified member of the human B7 family, designated B7 homolog 3 (B7-H3), that shares 20–27% amino acid identity with other B7 family members. B7-H3 mRNA is not detectable in peripheral blood mononuclear cells, although it is found in various normal tissues and in several tumor cell lines. Expression of B7-H3 protein, however, can be induced on dendritic cells (DCs) and monocytes by inflammatory cytokines and a combination of phorbol myristate acetate (PMA) + ionomycin. Soluble B7-H3 protein binds a putative counter-receptor on activated T cells that is distinct from CD28, cytotoxic T lymphocyte antigen 4 (CTLA-4), inducible costimulator (ICOS) and PD-1. B7-H3 costimulates proliferation of both CD4+ and CD8+ T cells, enhances the induction of cytotoxic T cells and selectively stimulates interferon γ (IFN-γ) production in the presence of T cell receptor signaling. In contrast, inclusion of antisense B7-H3 oligonucleotides decreases the expression of B7-H3 on DCs and inhibits IFN-γ production by DC-stimulated allogeneic T cells. Thus, we describe a newly identified costimulatory pathway that may participate in the regulation of cell-mediated immune responses.

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Figure 1: Putative amino acid sequence of human B7-H3 and alignment of B7 family members.
Figure 2: Northern blot analysis of B7-H3 mRNA.
Figure 3: Analysis of B7-H3 expression by flow cytometry.
Figure 4: Binding of B7-H3–Ig to activated T cells.
Figure 5: B7-H3 costimulates T cell growth and enhances CTL generation.
Figure 6: B7-H3 augments the expression of IFN-γ.
Figure 7: Inhibition of B7-H3 expression on DCs and IFN-γ production from DC-activated allogeneic T cells by B7-H3 antisense oligonucleotides.

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Acknowledgements

Supported by the Mayo Foundation and grants from the National Institutes of Health (NIH) (to L. C.), NIH postdoctoral training grant CA09127 (to A. I. C. and G. Z.), the US Army Breast Cancer Research Program postdoctoral fellowship (to K. T.) and NIH predoctoral training grant AI07425 (to J. S. L.). We thank K. Jensen for editing the manuscript.

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Authors and Affiliations

  1. Department of Immunology, Mayo Graduate and Medical Schools, Mayo Clinic, 200 First St. SW, Rochester, 55905, MN, USA

    Andrei I. Chapoval, Julie S. Lau, Ryan A. Wilcox, Dallas B. Flies, Haidong Dong, Gabriel L. Sica, Gefeng Zhu, Koji Tamada & Lieping Chen

  2. Human Genome Sciences Inc., Rockville, 20850, MD, USA

    Jian Ni & Ding Liu

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Correspondence to Lieping Chen.

Supplementary information

Web Figure 1.

Expression of B7-H3 on DCs. Monocyte-derived DCs were generated as described in the Methods, treated with either IFN-γ (left column) or PMA + ionomycin (right column) at indicated concentration for 24 h and subsequently stained with anti-B7-H3. (GIF 33 kb)

Web Figure 2.

Expression of B7-H3 on CD14+ cells. CD14+ monocytes were isolated from peripheral blood mononuclear cells of healthy donors and stimulated with either GM-CSF (left column) or PMA + ionomycin (right column) at indicated concentration for 24 h and subsequently stained with anti-B7-H3. (GIF 27 kb)

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Chapoval, A., Ni, J., Lau, J. et al. B7-H3: A costimulatory molecule for T cell activation and IFN-γ production. Nat Immunol 2, 269–274 (2001). https://doi.org/10.1038/85339

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