Cosgrove D, Chan S H, Waltzinger C, Benoist C, Mathis D
Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS, Unité 184 de Biologie Moléculaire et de Génie Génétique de l'INSERM, Faculté de Médecine, Strasbourg, France.
Int Immunol. 1992 Jun;4(6):707-10. doi: 10.1093/intimm/4.6.707.
Our aim was to assess the generality of the observation that positive selection of CD4+ T cells is mediated by MHC class II molecules on epithelial cells of the thymic cortex. By appropriate matings of previously established transgenic and mutant mouse lines, we were able to produce animals that lacked MHC class II molecules; individuals expressing only the class II E complex, but in all the usual thymic compartments; animals that had E molecules in the thymic medulla but not in the cortex; and, reciprocally, individuals expressing the E complex in the thymic cortex but essentially not in the medulla. Those mice which displayed class II molecules in the cortex had normal numbers of CD4+CD8- T cells in the thymus and CD4+ T cells in the periphery, while 'bare' cortex mice were almost devoid of mature CD4 single positive cells. This finding serves to generalize observations from previous studies of similar design but limited to assaying positive selection of T cells which expressed a single transgenic E-restricted TCR or a subset of V beta 6+ TCRs.
CD4+ T细胞的阳性选择是由胸腺皮质上皮细胞上的MHC II类分子介导的。通过先前建立的转基因和突变小鼠品系进行适当交配,我们能够培育出缺乏MHC II类分子的动物;仅在所有正常胸腺区室中表达II类E复合体的个体;胸腺髓质中有E分子但皮质中没有的动物;以及相反地,在胸腺皮质中表达E复合体但在髓质中基本不表达的个体。那些在皮质中显示II类分子的小鼠胸腺中CD4+CD8- T细胞数量正常,外周血中CD4+ T细胞数量正常,而“无皮质”小鼠几乎没有成熟的CD4单阳性细胞。这一发现有助于推广先前类似设计研究的观察结果,但之前的研究仅限于检测表达单一转基因E限制性TCR或V beta 6+ TCR子集的T细胞的阳性选择。