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

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

Research output: Contribution to journalArticle

533 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)269-274
Number of pages6
JournalNature Immunology
Volume2
Issue number3
DOIs
StatePublished - Mar 1 2001

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Chapoval, A. I., Ni, J., Lau, J. S., Wilcox, R. A., Flies, D. B., Liu, D., Dong, H., Sica, G. L., Zhu, G., Tamada, K., & Chen, L. (2001). B7-H3: A costimulatory molecule for T cell activation and IFN-γ production. Nature Immunology, 2(3), 269-274. https://doi.org/10.1038/85339