Yada S, Kishihara K, Kong Y Y, Nomoto K
Department of Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
J Immunol. 1998 Sep 1;161(5):2208-16.
CD45 is a transmembrane protein tyrosine phosphatase essential for Ag receptor-mediated signaling in both T and B cells. In this study we investigated roles of CD45 in development and cytolytic activities of murine intestinal intraepithelial lymphocytes (i-IEL) using CD45 exon 6 knockout (CD45-/-) mice. Interestingly, the total cell number of i-IEL was significantly reduced in CD45-/-mice during aging (10-20 wk of age), whereas the i-IEL number was normally increased in the wild-type littermates. Especially, the number of gamma(delta)TCR+ i-IEL decreased markedly in CD45-/- mice during aging. The i-IEL in CD45-/- mice were more susceptible to in vitro spontaneous apoptosis than the normal i-IEL, implying that CD45 is required for maintenance of the cellularity of i-IEL. Results from in vivo analyses of the extrathymic and intrathymic development of i-IEL suggested that CD45-mediated signaling is required for the intrathymic, but not the extrathymic, development of i-IEL. Moreover, the whole i-IEL from CD45-/- mice showed a significantly reduced cytolytic activity, and the residual cytolytic activity was completely diminished by depleting CD45+ i-IEL, suggesting that CD45 is indispensable for the TCR-mediated cytolytic activity of i-IEL. Furthermore, we found differential contributions of CD45 and p56lck to development and induction of cytolytic activities of i-IEL.
CD45是一种跨膜蛋白酪氨酸磷酸酶，对T细胞和B细胞中抗原受体介导的信号传导至关重要。在本研究中，我们使用CD45外显子6敲除（CD45-/-）小鼠，研究了CD45在小鼠肠道上皮内淋巴细胞（i-IEL）发育和细胞溶解活性中的作用。有趣的是，在衰老过程中（10-20周龄），CD45-/-小鼠的i-IEL总细胞数显著减少，而野生型同窝小鼠的i-IEL数量正常增加。特别是，衰老过程中CD45-/-小鼠的γδTCR+i-IEL数量明显减少。与正常i-IEL相比，CD45-/-小鼠的i-IEL对体外自发凋亡更敏感，这意味着维持i-IEL的细胞数量需要CD45。对i-IEL胸腺外和胸腺内发育的体内分析结果表明，i-IEL的胸腺内发育需要CD45介导的信号传导，但胸腺外发育则不需要。此外，来自CD45-/-小鼠的整个i-IEL显示出显著降低的细胞溶解活性，通过耗尽CD45+i-IEL，残余的细胞溶解活性完全消失，这表明CD45对于i-IEL的TCR介导的细胞溶解活性是不可或缺的。此外，我们发现CD45和p56lck对i-IEL发育和细胞溶解活性诱导的贡献不同。
