Ohteki T, Maki C, Koyasu S
Department of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
J Immunol. 2001 Jun 1;166(11):6509-13. doi: 10.4049/jimmunol.166.11.6509.
Mice lacking IFN-regulatory factor (IRF)-1 have reduced numbers of mature CD8+ T cells within the thymus and peripheral lymphoid organs, suggesting a critical role of IRF-1 in CD8(+) T cell differentiation. Here we show that endogenous Bcl-2 expression is substantially reduced in IRF-1(-/-)CD8+ thymocytes and that introduction of a human Bcl-2 transgene driven by Emu or lck promoter in IRF-1(-/-) mice restores the CD8(+) T cell development. Restored CD8+ T cells are functionally mature in terms of allogeneic MLR and cytokine production. In contrast to thymus-derived CD8+ T cells, other lymphocyte subsets including NK, NK T, and TCR-gammadelta(+) intestinal intraepithelial lymphocytes, which are also impaired in IRF-1(-/-) mice, are not rescued by expressing human Bcl-2. Our results indicate that IRF-1 differentially regulates the development of these lymphocyte subsets and that survival signals involving Bcl-2 are critical for the development of thymus-dependent CD8+ T cells.
缺乏干扰素调节因子（IRF）-1的小鼠胸腺和外周淋巴器官内成熟CD8+ T细胞数量减少，这表明IRF-1在CD8(+) T细胞分化中起关键作用。我们在此表明，IRF-1(-/-) CD8+胸腺细胞中内源性Bcl-2表达大幅降低，并且在IRF-1(-/-)小鼠中引入由Emu或lck启动子驱动的人Bcl-2转基因可恢复CD8(+) T细胞发育。就同种异体混合淋巴细胞反应（MLR）和细胞因子产生而言，恢复的CD8+ T细胞在功能上是成熟的。与胸腺来源的CD8+ T细胞不同，包括NK、NK T和TCR-γδ(+)肠上皮内淋巴细胞在内的其他淋巴细胞亚群在IRF-1(-/-)小鼠中也受损，但通过表达人Bcl-2并不能挽救它们。我们的结果表明，IRF-1对这些淋巴细胞亚群的发育有不同的调节作用，并且涉及Bcl-2的存活信号对胸腺依赖性CD8+ T细胞的发育至关重要。
