B7-H4, a molecule of the B7 family, negatively regulates T cell immunity
B7-H4, a molecule of the B7 family, negatively regulates T cell immunity
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DOI：
10.1016/s1074-7613(03)00152-3
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发表时间：
2003-06-01
期刊：
影响因子：
32.4
通讯作者：
Chen, LP
中科院分区：
文献类型：
--
作者：
Sica, GL;Choi, IH;Chen, LP
通过蛋白质序列分析和比较分子建模，我们确定了一个B7家族分子B7-H4。虽然B7-H4基因在小鼠和人的外周组织中广泛分布，但B7-H4蛋白在细胞表面的表达是有限的，并且在造血细胞上表现出诱导模式。B7-H4受体可在活化的T细胞上上调。通过阻断细胞周期，B7-H4结扎对T细胞的生长、细胞因子的分泌和细胞毒作用的发展具有深远的抑制作用。小鼠体内注射B7-H4Ig可削弱抗原特异性T细胞反应，而特异性单抗阻断内源性B7-H4可促进T细胞反应。因此，B7-H4可能参与了外周组织细胞免疫的负调控。
We identify a B7 family molecule, B7-H4, by protein sequence analysis and comparative molecular modeling. While B7-H4 mRNA is widely distributed in mouse and human peripheral tissues, cell surface expression of B7-H4 protein is limited and shows an inducible pattern on hematopoietic cells. Putative receptor of B7-H4 can be upregulated on activated T cells. By arresting cell cycle, B7-H4 ligation of T cells has a profound inhibitory effect on the growth, cytokine secretion, and development of cytotoxicity. Administration of B7-H4Ig into mice impairs antigen-specific T cell responses whereas blockade of endogenous B7-H4 by specific monoclonal antibody promotes T cell responses. B7-H4 thus may participate in negative regulation of cell-mediated immunity in peripheral tissues.