Williams O, Norton T, Halligey M, Kioussis D, Brady H J
Division of Molecular Immunology, Medical Research Council, National Institute for Medical Research, London, United Kingdom.
J Exp Med. 1998 Sep 21;188(6):1125-33. doi: 10.1084/jem.188.6.1125.
T cell development and selection in the thymus are shaped by the induction of apoptosis. However, a direct role in T cell development and selection for any of the molecules known to regulate apoptosis has remained controversial. We have studied the effect of bax and bcl-2 transgenes in recombination activation gene 1-deficient (RAG-1(-/-)) mice transgenic for the major histocompatibility complex class I-restricted F5 T cell receptor. Overexpression of a bax transgene in the thymus seriously impairs the production of mature T cells, whereas bcl-2 overexpression greatly promotes it. The effect of bax and bcl-2 overexpression on antigen-induced negative selection was studied using fetal thymic organ cultures. This analysis showed that Bcl-2 strongly inhibits negative selection, whereas Bax does not affect it. Our data directly show that Bcl-2 family members have specific roles in T cell selection and also lend support to the hypothesis that Bax and Bcl-2 can antagonize each other's action in a certain apoptosis pathway while in another they can be functionally nonreciprocal.
胸腺中T细胞的发育和选择受细胞凋亡诱导的影响。然而，已知调节细胞凋亡的任何分子在T细胞发育和选择中的直接作用仍存在争议。我们研究了bax和bcl-2转基因在主要组织相容性复合体I类限制性F5 T细胞受体转基因的重组激活基因1缺陷（RAG-1(-/-)）小鼠中的作用。胸腺中bax转基因的过表达严重损害成熟T细胞的产生，而bcl-2过表达则极大地促进其产生。使用胎胸腺器官培养研究了bax和bcl-2过表达对抗原诱导的阴性选择的影响。该分析表明，Bcl-2强烈抑制阴性选择，而Bax不影响它。我们的数据直接表明，Bcl-2家族成员在T细胞选择中具有特定作用，也支持了Bax和Bcl-2在某些凋亡途径中可以相互拮抗作用而在另一些途径中它们在功能上可能是非相互的这一假说。
