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

We describe here a newly identified member of the human B7 family, designat ed 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 mononuc lear cells, although it is found in various normal tissues and in several t umor cell lines. Expression of B7-H3 protein, however, can be induced on de ndritic cells (DCs) and monocytes by inflammatory cytokines and a combinati on of phorbol myristate acetate (PMA) + ionomycin, Soluble B7-H3 protein bi nds a putative counter-receptor on activated T cells that is distinct from CD28, cytotoxic T lymphocyte antigen 4 (CTLA-4), inducible costimulator (IC OS) and PD-1. B7-H3 costimulates proliferation of both CD4(+) and CD8(+) T cells, enhances the induction of cytotoxic T cells and selectively stimulat es interferon gamma (IFN-gamma) production in the presence of T cell recept or signaling. In contrast, inclusion of antisense B7-H3 oligonucleotides de creases the expression of B7-H3 on DCs and inhibits IFN-gamma production by DC-stimutated allogeneic T cells. Thus, we describe a newly identified cos timulatory pathway that may participate in the regulation of cell-mediated immune responses.