Chan S H, Cosgrove D, Waltzinger C, Benoist C, Mathis D
Laboratoire de Génétique Moléculaire, Eucaryotes du Centre National de la Recherche Scientifique, Faculté de Médecine, Strasbourg, France.
Cell. 1993 Apr 23;73(2):225-36. doi: 10.1016/0092-8674(93)90225-f.
Thymocyte commitment to the CD4 helper versus CD8 cytotoxic lineage has not been satisfactorily established. Two models have been elaborated: one based on instruction, the other on selection. Most previous results support the instructive model, but our comparison of thymocyte differentiation in MHC class II-, class I- and double-deficient mice provides data challenging it. There exists a significant population of CD4 single positive cells in class II-deficient animals that is intermediate in maturity between CD4+CD8+ and end-stage CD4+CD8- thymocytes and is selected on class I molecules; an equivalent CD8+CD4- population occurs in class I-deficient animals. We propose a selective model entailing two TCR-MHC molecule engagements: the first provokes random down-modulation of either CD4 or CD8 and a degree of differentiation; the second, requiring participation of the appropriate coreceptor, permits end-stage differentiation.
胸腺细胞向CD4辅助性细胞谱系或CD8细胞毒性细胞谱系的定向尚未得到令人满意的确立。已经阐述了两种模型：一种基于指令，另一种基于选择。以前的大多数结果支持指令性模型，但我们对MHC II类、I类和双缺陷小鼠中胸腺细胞分化的比较提供了挑战该模型的数据。在II类缺陷动物中存在大量CD4单阳性细胞群体，其成熟度介于CD4+CD8+和终末阶段CD4+CD8-胸腺细胞之间，并在I类分子上被选择；在I类缺陷动物中出现了等效的CD8+CD4-群体。我们提出了一种选择性模型，该模型需要两个TCR-MHC分子结合：第一个引起CD4或CD8的随机下调和一定程度的分化；第二个需要适当的共受体参与，允许终末分化。
