Tamura H, Dong H, Zhu G, Sica G L, Flies D B, Tamada K, Chen L
Department of Immunology, Mayo Graduate and Medical Schools, Mayo Clinic, Rochester, MN 55905, USA.
Blood. 2001 Mar 15;97(6):1809-16. doi: 10.1182/blood.v97.6.1809.
B7-H1 is a recently described B7-like molecule that costimulates T-cell growth and cytokine secretion without binding to CD28, cytotoxic T-lymphocyte antigen-4 (CTLA-4), and inducible costimulator (ICOS). In this report, a mouse homologue of human B7-H1 is identified, and its immunologic functions are studied in vitro and in vivo. Mouse B7-H1 shares 69% amino acid homology to the human counterpart. Similar to human B7-H1, mouse B7-H1 can be induced to express on macrophages, T cells, and B cells and to enhance T-cell proliferation and secretion of interleukin-10 (IL-10), interferon-gamma, and granulocyte-macrophage colony-stimulating factor but not IL-2 and IL-4. Furthermore, B7-H1 preferentially costimulates CD4+ T cells independently of CD28 and enhances mixed lymphocyte responses to allogeneic antigens. In contrast to B7-1, expression of B7-H1 on murine P815 tumor cells by transfection fails to increase allogeneic and syngeneic cytolytic T-cell responses in vitro and in vivo. Administration of B7-H1Ig fusion protein, however, enhances keyhole limpet hemocyanin- specific T-cell proliferation and 2,4,6-trinitrophenyl-specific immunoglobulin G2a antibody production. The study thus identifies a unique costimulatory pathway that preferentially affects T-helper cell functions.
B7-H1是一种最近被描述的B7样分子，它能共刺激T细胞生长和细胞因子分泌，而不与CD28、细胞毒性T淋巴细胞抗原4（CTLA-4）和诱导性共刺激分子（ICOS）结合。在本报告中，鉴定了人B7-H1的小鼠同源物，并在体外和体内研究了其免疫功能。小鼠B7-H1与人B7-H1的氨基酸同源性为69%。与人类B7-H1相似，小鼠B7-H1可被诱导在巨噬细胞、T细胞和B细胞上表达，并增强T细胞增殖以及白细胞介素10（IL-10）、干扰素-γ和粒细胞-巨噬细胞集落刺激因子的分泌，但不增强IL-2和IL-4的分泌。此外，B7-H1优先独立于CD28共刺激CD4+T细胞，并增强对同种异体抗原的混合淋巴细胞反应。与B7-1不同，通过转染在鼠P815肿瘤细胞上表达B7-H1在体外和体内均不能增加同种异体和同基因溶细胞性T细胞反应。然而，给予B7-H1Ig融合蛋白可增强钥孔戚血蓝蛋白特异性T细胞增殖和2,4,6-三硝基苯特异性免疫球蛋白G2a抗体的产生。因此，该研究确定了一条独特的共刺激途径，该途径优先影响辅助性T细胞功能。
