Yamashita Y, Hooker S W, Jiang H, Laurent A B, Resta R, Khare K, Coe A, Kincade P W, Thompson L F
Immunobiology and Cancer Program, Oklahoma Medical Research Foundation, Oklahoma City 73104, USA.
Eur J Immunol. 1998 Oct;28(10):2981-90. doi: 10.1002/(SICI)1521-4141(199810)28:10<2981::AID-IMMU2981>3.0.CO;2-D.
CD73 is a glycosyl phosphatidylinositol-anchored protein with both ecto-enzyme activity (ecto-5'-nucleotidase) and signal transducing capabilities for human T lymphocytes. We now report an analysis of the distribution and function of CD73 in murine lymphoid tissues made possible by the development of the first monoclonal antibodies (mAb) specific for murine CD73. Subsets of T and B lymphocytes are CD73+ and the level of expression increases with lymphocyte maturation in both species. Among B cells, CD73 is largely restricted to cells which have undergone isotype switching. The signal transmitting function of CD73 is also conserved, as splenic T cells treated with anti-CD73 mAb plus phorbol 12-myristate 13-acetate proliferate and secrete IL-2. Fyn-/- mice are unresponsive to CD73 ligation, however, demonstrating the requirement for this tyrosine kinase in CD73-mediated signal transduction. CD73 is down-regulated after mAb plus cross-linking, suggesting that expression may be controlled by interaction with a ligand. Only small numbers of thymocytes are CD73+, so CD73 receptor functions are unlikely to be important for developing T cells. However, immunohistochemical analysis reveals that reticular and vascular cells throughout the thymus and other lymphoid tissues are markedly CD73+. Therefore, CD73 might mediate lymphocyte-stromal cell interactions or condition the local microenvironment to facilitate lymphocyte development and/or function.
CD73是一种糖基磷脂酰肌醇锚定蛋白，具有胞外酶活性（胞外5'-核苷酸酶）以及对人T淋巴细胞的信号转导能力。我们现在报告了对CD73在小鼠淋巴组织中的分布和功能的分析，这得益于针对小鼠CD73的首个单克隆抗体（mAb）的开发。T淋巴细胞和B淋巴细胞亚群均为CD73阳性，并且在这两个物种中，随着淋巴细胞成熟，其表达水平会升高。在B细胞中，CD73主要局限于已经发生同种型转换的细胞。CD73的信号传递功能也具有保守性，因为用抗CD73 mAb加佛波醇12-肉豆蔻酸酯13-乙酸酯处理的脾T细胞会增殖并分泌白细胞介素-2。然而，Fyn基因敲除小鼠对CD73连接无反应，这表明在CD73介导的信号转导中需要这种酪氨酸激酶。mAb加交联后CD73表达下调，这表明其表达可能受与配体相互作用的控制。只有少数胸腺细胞是CD73阳性，因此CD73受体功能对发育中的T细胞不太可能重要。然而，免疫组织化学分析显示，整个胸腺和其他淋巴组织中的网状细胞和血管细胞明显为CD73阳性。因此，CD73可能介导淋巴细胞与基质细胞的相互作用，或调节局部微环境以促进淋巴细胞的发育和/或功能。
