Linette G P, Grusby M J, Hedrick S M, Hansen T H, Glimcher L H, Korsmeyer S J
Howard Hughes Medical Institute, Department of Medicine and Pathology, Washington University School of Medicine, St. Louis, Missouri 63110.
Immunity. 1994 Jun;1(3):197-205. doi: 10.1016/1074-7613(94)90098-1.
In vivo thymocyte maturation models were used to investigate the differentiation role of Bcl-2. In alpha/beta T cell receptor (TCR) class II-restricted transgenic mice, Bcl-2 was upregulated at the CD4+ CD8+ stage during positive selection. The lckpr-bcl2 transgene was bred onto MHC classes I-I- and II-I-, MHC-I-, and alpha/beta TCR backgrounds to determine whether Bcl-2 promoted thymocyte maturation in the absence of coreceptor-MHC interaction. Bcl-2 rescued CD8+ thymocytes in class I-I- and alpha/beta TCR in mice; however, they were not exported to the periphery. Bcl-2 had no effect on CD4 lineage maturation in class II-I- mice. No single-positive thymocytes accumulate in MHC-I- mice despite overexpressed Bcl-2. Thus, Bcl-2 enables selection of certain TCRs on class II molecules and their differentiation along the CD8 pathway; however, Bcl-2 did not substitute for positive selection. In RAG-1-I- mice, Bcl-2 promoted differentiation to the CD4+ CD8+ stage. Bcl-2 can promote thymocyte maturation at several control points.
体内胸腺细胞成熟模型被用于研究Bcl-2的分化作用。在α/β T细胞受体（TCR）II类限制性转基因小鼠中，Bcl-2在阳性选择过程中的CD4+ CD8+阶段上调。将lckpr-bcl2转基因培育到MHC I类-I-和II类-I-、MHC-I-以及α/β TCR背景上，以确定在缺乏共受体-MHC相互作用的情况下Bcl-2是否促进胸腺细胞成熟。Bcl-2拯救了I类-I-小鼠和α/β TCR小鼠中的CD8+胸腺细胞；然而，它们并未输出到外周。Bcl-2对II类-I-小鼠中的CD4谱系成熟没有影响。尽管Bcl-2过表达，但在MHC-I-小鼠中没有单阳性胸腺细胞积累。因此，Bcl-2能够选择II类分子上的某些TCR并使其沿CD8途径分化；然而，Bcl-2不能替代阳性选择。在RAG-1-I-小鼠中，Bcl-2促进向CD4+ CD8+阶段的分化。Bcl-2可以在几个控制点促进胸腺细胞成熟。
