THE FAS ANTIGEN IS INVOLVED IN PERIPHERAL BUT NOT THYMIC DELETION OF T-LYMPHOCYTES IN T-CELL RECEPTOR TRANSGENIC MICE
THE FAS ANTIGEN IS INVOLVED IN PERIPHERAL BUT NOT THYMIC DELETION OF T-LYMPHOCYTES IN T-CELL RECEPTOR TRANSGENIC MICE
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DOI：
10.1016/1074-7613(94)90067-1
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发表时间：
1994-08-01
期刊：
影响因子：
32.4
通讯作者：
ABBAS, AK
中科院分区：
文献类型：
--
作者：
SINGER, GG;ABBAS, AK
通过将鸽细胞色素c 81-104肽特异性的转基因T细胞受体培育到Fas缺陷型MRL-lpr/lpr和对照MRL（+/+）小鼠中，分析了细胞死亡相关基因fas在T淋巴细胞发育和对抗原应答中的作用。转基因表达T细胞在两种菌株中正常成熟，并以正常数量分布在外周淋巴组织中。来自lpr/lpr小鼠的成熟CD 4（+）T细胞对高剂量抗原的抑制和凋亡性细胞死亡具有抗性。肽抗原的体内给药引起MRL-lpr/lpr和MRL（+/+）菌株中胸腺T细胞的缺失。相比之下，抗原诱导的外周T细胞缺失发生在MRL（+/+）中，但不发生在MRL-lpr/lpr菌株中。因此，Fas基因在成熟T淋巴细胞活化诱导的细胞死亡中起重要作用，但在胸腺未成熟细胞的负选择中不起作用。
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.