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
Department of Immunology, Mayo Graduate and Medical Schools, Mayo Clinic, Rochester, MN 55905, USA.
Nat Immunol. 2001 Mar;2(3):269-74. doi: 10.1038/85339.
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 gamma (IFN-gamma) 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-gamma 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.
我们在此描述人类B7家族一个新鉴定出的成员，命名为B7同源物3（B7-H3），它与其他B7家族成员有20%-27%的氨基酸序列相同。尽管在多种正常组织和几种肿瘤细胞系中能检测到B7-H3 mRNA，但在外周血单核细胞中却检测不到。然而，炎性细胞因子以及佛波酯肉豆蔻酸酯乙酸酯（PMA）+离子霉素的组合可诱导树突状细胞（DC）和单核细胞表达B7-H3蛋白。可溶性B7-H3蛋白与活化T细胞上一种假定的反受体结合，该反受体不同于CD28、细胞毒性T淋巴细胞抗原4（CTLA-4）、诱导性共刺激分子（ICOS）和程序性死亡受体1（PD-1）。B7-H3共刺激CD4+和CD8+ T细胞增殖，增强细胞毒性T细胞的诱导，并在存在T细胞受体信号的情况下选择性刺激干扰素γ（IFN-γ）产生。相反，加入反义B7-H3寡核苷酸会降低DC上B7-H3的表达，并抑制DC刺激的同种异体T细胞产生IFN-γ。因此，我们描述了一条新鉴定出的共刺激途径，它可能参与细胞介导的免疫反应的调节。
