The Role of CD45 in Leukocyte Differentiation and Function

本研究以CD45外显子6缺陷小鼠(CD45-/-小鼠)为研究对象，分析了CD45在T、B和NK细胞发育、激活和功能中的作用。在CD45-T细胞受体(TCR)转基因CD45小鼠的分析中，提示CD45参与了T细胞阳性选择和TCRα链等位基因排斥的信号转导。来自CD45-/-小鼠的CD45缺陷胸腺细胞和外周成熟T细胞对TCR-交联物几乎没有反应，这表明CD45对于TCR介导的信号机制至关重要。此外，在CD45-/-小鼠的CD45^-T细胞中未观察到包括溶细胞T淋巴细胞和辅助性T细胞功能在内的抗原特异性反应。此外，CD45还参与了表皮和胎儿胸腺中VGamma3T细胞成熟过程中的信号转导。CD45-/-小鼠一生中B细胞的发育都得到了促进(脾中B细胞(Sigm^+)的数量大约增加了一倍)。CD45-/-小鼠的CD45缺陷B细胞表现出完整的B细胞功能，包括T依赖和非依赖的抗原特异性抗体的产生和体内的分类转换，如果将正常的CD45^+T细胞过继地转移到敲除小鼠中，CD45-/-小鼠的脾细胞的NK活性明显增强，因为CD45-/-小鼠的NK细胞数量增加。NK和LAK细胞表面无CD45表达，但杀伤活性和ADCC活性保持不变。由此可见，CD45在T、B和NK细胞中对发育和功能的需求是不同的。

We have analyzed the involvement of CD45 in development, activation and function of T,B and NK cells using CD45 exon 6-deficient mice (CD45-/-mice) in this research project.In the analysis of CD45-deicient T cell receptor (TCR)-transgenic CD45 mice, it was suggested that CD45 is involved in the signal transduction for positive selection of T cells and allelic exclusion of TCRalpha chain. CD45-defective thymocytes and peripheral mature T cells from CD45-/- mice showed virtually no response to TCR-crosslinking suggesting that CD45 is crucial for a TCR-mediated signaling mechanism. Furthermore, Antigen-specific response including cytolytic T lymphocyte and helper T cell function could not observed in CD45^- T cells from CD45-/- mice. Moreover, it was demonstrated that CD45 is involved in the signal transduction during maturation of Vgamma3 T cells in epidermis and fetal thymus.B cell development in the CD45-/- mice was enhanced throughout their lives (the approximately twice more increased number of B cells (sIgM^+) in the spleen). CD45-defective B cells from CD45-/-mice showed intact B cell functions including T -dependent and -independent antigen-specific antibody production and class switching in vivo if normal CD4^+ T cells were adoptively transferred into the knock out mice.The NK activity of the splenocytes from CD45-/- mice was markedly elevated because of the increased number of NK cells in the CD45-/- mice. Cytolytic and ADCC activities were intact in the NK and LAK cells despite no CD45 surface expression.From the above data, it's clear that requirement of CD45 for development and function is different in T,B and NK cells.