Singer G G, Abbas A K
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
Immunity. 1994 Aug;1(5):365-71. doi: 10.1016/1074-7613(94)90067-1.
The role of a cell death-associated gene, fas, in T lymphocyte development and responses to antigen has been analyzed by breeding a transgenic T cell receptor specific for the 81-104 peptide of pigeon cytochrome c into fas-defective MRL-lpr/lpr and control MRL+/+ mice. Transgene-expressing T cells mature normally in both strains and populate peripheral lymphoid tissues in normal numbers. Mature CD4+ T cells from the lpr/lpr mice are resistant to suppression by high doses of antigen and to apoptotic cell death. In vivo administration of peptide antigen causes deletion of thymic T cells in both MRL-lpr/lpr and MRL+/+ strains. By contrast, antigen-induced deletion of peripheral T cells occurs in the MRL+/+ but not in the MRL-lpr/lpr strain. Therefore, the fas gene plays an essential role in activation-induced cell death in mature T lymphocytes, but not in the negative selection of immature cells in the thymus.
通过将对鸽细胞色素c的81 - 104肽具有特异性的转基因T细胞受体导入fas缺陷的MRL - lpr/lpr小鼠和对照MRL +/+小鼠中，分析了细胞死亡相关基因fas在T淋巴细胞发育及对抗原反应中的作用。表达转基因的T细胞在两种品系中均正常成熟，并以正常数量填充外周淋巴组织。来自lpr/lpr小鼠的成熟CD4 + T细胞对高剂量抗原的抑制作用和凋亡性细胞死亡具有抗性。体内给予肽抗原则会导致MRL - lpr/lpr和MRL +/+品系的胸腺T细胞缺失。相比之下，抗原诱导的外周T细胞缺失发生在MRL +/+品系中，而不是MRL - lpr/lpr品系中。因此，fas基因在成熟T淋巴细胞的激活诱导性细胞死亡中起重要作用，但在胸腺中未成熟细胞的阴性选择中不起作用。
