Nature Immunology
2, 269 - 274 (2001)
doi:10.1038/85339
B7-H3: A costimulatory molecule for T cell activation and IFN- productionAndrei I. Chapoval1, Jian Ni2, Julie S. Lau1, Ryan A. Wilcox1, Dallas B. Flies1, Ding Liu2, Haidong Dong1, Gabriel L. Sica1, Gefeng Zhu1, Koji Tamada1
& Lieping Chen11
Department of Immunology, Mayo Graduate and Medical Schools, Mayo Clinic, 200 First St. SW, Rochester, MN 55905, USA. 2
Human Genome Sciences Inc. Rockville, MD 20850, USA.
Correspondence should be addressed to Lieping Chen chen.lieping@mayo.eduWe 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  (IFN-) 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- 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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