错误选择的CD8 T细胞通过CD8基因甲基化和细胞死亡而失活
G A Pestano1, Y Zhou, L A Trimble
1Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston MA 02115, USA.
Science (New York, N.Y.)
|May 15, 1999
概括
错误选择的CD8细胞被一个后皮质质量控制机制清除. 无法激活T细胞受体 (TCRs) 和CD8核受体,会触发细胞亡,从而预防自身免疫性疾病.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 为了确保T细胞的正常功能,T细胞经历了胸膜选择.
- 错误选择的CD8细胞,缺乏MHC类I的T细胞受体 (TCR) 识别,可以逃避胸膜查.
- 存在关键的需要,以后thymic机制来消除这些潜在的自反应性T细胞.
研究的目的:
- 定义一种后皮质量控制机制,以清除错误选择的CD8细胞.
- 阐明导致 CD8 细胞与非功能性 TCRs 消除的分子事件.
- 了解自身免疫疾病的这种质量控制途径中缺陷的含义.
主要方法:
- 对CD8细胞种群的分析.
- 研究T细胞受体 (TCR) 和CD8核受体的参与.
- 评估基因表达变化,包括通过再甲基化抑制CD8基因.
- 评估表面Fas和Fas连接物的上调.
- 诱导和分析细胞亡.
主要成果:
- 错误选择的CD8细胞无法同时与MHC分子接触其TCR和CD8核受体.
- 这种失败启动了一个过程,涉及通过再甲基化抑制CD8基因表达.
- 这个过程的高潮是表面Fas和Fas连接体的上调,导致了细胞灭绝.
- 持续的TCR-CD8与MHC的共同接触作为生存检查点.
结论:
- 一种新的后皮质量控制途径消除了具有非功能性TCR的CD8细胞.
- 这一途径依赖于TCR和CD8核受体与MHC的协调参与.
- 这种死亡信号通路中的分子缺陷有助于双阴性T细胞的扩张和全身自身免疫性疾病.
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