Li Wei, Kim Moon-Gyo, Gourley Tania S, McCarthy Brian P, Sant'Angelo Derek B, Chang Cheong-Hee
Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana 46202.
Immunity. 2005 Oct;23(4):375-86. doi: 10.1016/j.immuni.2005.09.002.
Conventional understanding of CD4 T cell development is that the MHC class II molecules on cortical thymic epithelial cell are necessary for positive selection, as demonstrated in mouse models. Clinical data, however, show that hematopoietic stem cells reconstitute CD4 T cells in patients devoid of MHC class II. Additionally, CD4 T cells generated from human stem cells in immunocompromised mice were restricted to human, but not mouse, MHC class II. These studies suggest an alternative pathway for CD4 T cell development that does not normally exist in mice. MHC class II is expressed on developing human thymocytes, indicating a possible role of MHC II on thymocytes for CD4 T cell generation. Therefore, we created mice in which MHC class II is expressed only on T lineage cells. Remarkably, the CD4 compartment in such mice is efficiently reconstituted with unique specificity, demonstrating a novel thymocyte-driven pathway of CD4 T cell selection.
对CD4 T细胞发育的传统理解是，如在小鼠模型中所证实的那样，皮质胸腺上皮细胞上的II类主要组织相容性复合体（MHC）分子对于阳性选择是必需的。然而，临床数据显示，造血干细胞可在缺乏II类MHC的患者体内重建CD4 T细胞。此外，在免疫受损小鼠中由人类干细胞产生的CD4 T细胞仅限于人类而非小鼠的II类MHC。这些研究提示了一种在小鼠中通常不存在的CD4 T细胞发育的替代途径。II类MHC在发育中的人类胸腺细胞上表达，表明II类MHC在胸腺细胞上对于CD4 T细胞生成可能发挥作用。因此，我们构建了仅在T细胞谱系细胞上表达II类MHC的小鼠。值得注意的是，此类小鼠中的CD4细胞区室以独特的特异性被有效地重建，证明了一种新的胸腺细胞驱动的CD4 T细胞选择途径。
