Ong C J, Dutz J P, Chui D, Teh H S, Marth J D
Biomedical Research Centre, University of British Columbia, Vancouver, Canada.
Immunology. 1997 May;91(1):95-103. doi: 10.1046/j.1365-2567.1997.00216.x.
T-cell development is arrested at the CD4+CD8+ (DP; double-positive) stage of thymocyte development in CD45 null mice. However, the mechanism by which CD45 participates in the positive selection of T cells remains to be investigated. In this report we describe a DP thymocyte population that associates positive selection with expression of high levels of CD45, CD4 and CD8. DP thymocytes of this phenotype are large, cycling cells and represent approximately 20% of DP thymocytes in normal mice. In mice expressing a transgenic T-cell receptor (TCR) specific for the male antigen presented by H-2Db (H-Y TCR), the up-regulation of TCR, CD5 and CD69 in this large DP population occurred in a major histocompatibility complex (MHC)-restricted manner. To investigate further the role of CD45 in positive selection, we determined whether thymocytes that expressed a transgenic CD45RO molecule under the control of the proximal lck promoter can influence the positive selection of T cells in H-Y TCR transgenic mice. It was found that in female H-Y TCR transgenic mice, MHC-restricted positive selection of CD4- CD8+ H-Y TCR+ thymocytes was enhanced by increased CD45RO expression. Thus, CD45 increases the efficacy of positive selection of CD4- CD8+ thymocytes that express H-Y TCR.
在CD45基因敲除小鼠中，T细胞发育在胸腺细胞发育的CD4+CD8+（DP；双阳性）阶段停滞。然而，CD45参与T细胞阳性选择的机制仍有待研究。在本报告中，我们描述了一个双阳性胸腺细胞群体，其将阳性选择与高水平的CD45、CD4和CD8的表达联系起来。这种表型的双阳性胸腺细胞是大的循环细胞，在正常小鼠中约占双阳性胸腺细胞的20%。在表达对由H-2Db呈递的雄性抗原具有特异性的转基因T细胞受体（TCR）（H-Y TCR）的小鼠中，这个大的双阳性群体中TCR、CD5和CD69的上调以主要组织相容性复合体（MHC）限制的方式发生。为了进一步研究CD45在阳性选择中的作用，我们确定了在近端lck启动子控制下表达转基因CD45RO分子的胸腺细胞是否能影响H-Y TCR转基因小鼠中T细胞的阳性选择。结果发现，在雌性H-Y TCR转基因小鼠中，CD45RO表达的增加增强了CD4-CD8+H-Y TCR+胸腺细胞的MHC限制的阳性选择。因此，CD45提高了表达H-Y TCR的CD4-CD8+胸腺细胞阳性选择的效率。
