Agui T, Oka M, Yamada T, Sakai T, Izumi K, Ishida Y, Himeno K, Matsumoto K
Institute for Animal Experimentation, University of Tokushima School of Medicine, Japan.
J Exp Med. 1990 Dec 1;172(6):1615-24. doi: 10.1084/jem.172.6.1615.
A mutant strain (LEC) of rats was found to have a novel defect in T cell maturation, that is, arrest of differentiation from CD4+8+ to CD4+8- but not to CD4-8+ thymocytes. FACS analyses demonstrated a deficiency in the CD4+8- T cell subset in the thymus and a marked decrease in CD4+ T cells in peripheral lymphoid organs. Expression of the T cell receptor (TCR)/CD3 complex in CD4+8+ and CD4-8+ thymocytes of LEC rats was normal. Expression of class II major histocompatibility complex (MHC) in the thymus of LEC rats was also the same as that of normal rats. These results indicate that maturational arrest occurs only in the transition pathway from CD4+8+ to CD4+8- thymocytes, and that this mutation can not be attributed to the default of expression of either TCR/CD3, CD4, or class II MHC antigen. Consequently, dysfunction of helper T cells was observed in LEC rats, while killer T cells and B cells functioned normally. Although the complete identification of the origin of this mutation requires further studies, it is hoped that such investigations will throw light on the mechanism of positive selection.
发现大鼠的一种突变株(LEC)在T细胞成熟过程中存在一种新的缺陷,即从CD4+8+胸腺细胞向CD4+8-胸腺细胞的分化停滞,但向CD4-8+胸腺细胞的分化未停滞。流式细胞术分析表明,胸腺中CD4+8- T细胞亚群存在缺陷,外周淋巴器官中CD4+ T细胞显著减少。LEC大鼠CD4+8+和CD4-8+胸腺细胞中T细胞受体(TCR)/CD3复合物的表达正常。LEC大鼠胸腺中II类主要组织相容性复合体(MHC)的表达也与正常大鼠相同。这些结果表明,成熟停滞仅发生在从CD4+8+胸腺细胞到CD4+8-胸腺细胞的转变途径中,并且这种突变不能归因于TCR/CD3、CD4或II类MHC抗原表达的缺失。因此,在LEC大鼠中观察到辅助性T细胞功能障碍,而杀伤性T细胞和B细胞功能正常。虽然要完全确定这种突变的起源还需要进一步研究,但希望这样的研究将有助于阐明阳性选择的机制。