Yu Qing, Sen Jyoti Misra
Lymphocyte Development Unit, Laboratory of Immunology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
J Immunol. 2007 Apr 15;178(8):5028-34. doi: 10.4049/jimmunol.178.8.5028.
Positive selection and lineage commitment to the cytolytic or helper lineage of T cells result in coordinated expression of MHC class I-restricted TCR and CD8 coreceptor or MHC class II-restricted TCR and CD4 molecule. Positive selection signals also regulate the survival and generation of requisite numbers of cytolytic or Th cells. beta-Catenin is the major transcriptional cofactor of T cell factor and plays a role in thymocyte development. In this study, using mice expressing stabilized beta-catenin and mice with T cell-specific deletion of beta-catenin, we show that beta-catenin regulates positive selection, but not lineage commitment of thymocytes. Furthermore, beta-catenin expression accelerates the timing of mature CD8 thymocyte generation such that CD4 and CD8 single-positive thymocytes mature with the same kinetics during development.
T细胞向细胞毒性或辅助性谱系的阳性选择和谱系定向导致MHC I类限制性TCR和CD8共受体或MHC II类限制性TCR和CD4分子的协同表达。阳性选择信号还调节细胞毒性或Th细胞所需数量的存活和产生。β-连环蛋白是T细胞因子的主要转录辅因子,在胸腺细胞发育中起作用。在本研究中,我们使用表达稳定β-连环蛋白的小鼠和β-连环蛋白T细胞特异性缺失的小鼠,表明β-连环蛋白调节阳性选择,但不调节胸腺细胞的谱系定向。此外,β-连环蛋白的表达加速了成熟CD8胸腺细胞产生的时间,使得CD4和CD8单阳性胸腺细胞在发育过程中以相同的动力学成熟。