BCL-2 IS UP-REGULATED AT THE CD4(+)CD8(+) STAGE DURING POSITIVE SELECTION AND PROMOTES THYMOCYTE DIFFERENTIATION AT SEVERAL CONTROL POINTS
BCL-2 IS UP-REGULATED AT THE CD4(+)CD8(+) STAGE DURING POSITIVE SELECTION AND PROMOTES THYMOCYTE DIFFERENTIATION AT SEVERAL CONTROL POINTS
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DOI：
10.1016/1074-7613(94)90098-1
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发表时间：
1994-06-01
期刊：
影响因子：
32.4
通讯作者：
KORSMEYER, SJ
中科院分区：
文献类型：
--
作者：
LINETTE, GP;GRUSBY, MJ;KORSMEYER, SJ
采用体内胸腺细胞成熟模型，研究Bcl2的分化作用。在α/βT细胞受体(TCR)II类限制性转基因小鼠中，在阳性选择过程中，Bcl-2在CD4(+)CD8(+)阶段上调。将LCK(PR)-BCL2转基因基因培养到MHC I--/-和II-/-、MHC(-/-)和α/βTCR背景上，以确定在没有辅助受体-MHC相互作用的情况下，Bcl-2是否促进胸腺细胞的成熟。在I--/-和α/βTCR小鼠中，bcl2挽救了CD8(+)胸腺细胞；然而，它们并没有输出到外周。BCL-2对II-/-小鼠的CD4谱系成熟没有影响。尽管Bcl2过表达，MHC(-/-)小鼠体内没有单一阳性胸腺细胞积聚。因此，Bcl-2可以选择II类分子上的某些TCR，并使其沿着CD8途径分化，但并不能替代正向选择。在RAG-1(-/-)小鼠中，Bcl2促进分化为CD4(+)CD8(+)阶段。BCL-2可在多个控制点促进胸腺细胞成熟。
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 lck(pr)-bcl2 transgene was bred onto MHC classes I--/- and II-/-, MHC(-/-), 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--/- and alpha/beta TCR mice; however, they were not exported to the periphery. Bcl-2 had no effect an CD4 lineage maturation in class II-/- mice. No single-positive thymocytes accumulate in MHC(-/-) 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(-/-) mice, Bcl-2 promoted differentiation to the CD4(+)CD8(+) stage. Bcl-2 can promote thymocyte maturation at several control points.