Ma A, Pena J C, Chang B, Margosian E, Davidson L, Alt F W, Thompson C B
Howard Hughes Medical Institute, Children's Hospital, Boston, MA, USA.
Proc Natl Acad Sci U S A. 1995 May 23;92(11):4763-7. doi: 10.1073/pnas.92.11.4763.
The bclx gene has been shown to regulate programmed cell death in vitro. We now show that Bclx expression increases dramatically when T cells differentiate from CD4- CD8- (double negative) thymocytes to CD4+ CD8+ [double positive (DP)] thymocytes. In contrast single-positive (SP) thymocytes express negligible amounts of Bclx protein. This expression pattern contrasts with that of Bcl2, which is present in double-negative thymocytes, down-regulated in DP thymocytes, and reinduced upon maturation to SP thymocytes. Elimination of Bclx by gene targeting dramatically shortens the survival of DP thymocytes but not the survival of SP thymocytes or peripheral SP T cells. These data suggest that the induction of Bclx during thymic maturation plays a critical role in regulating the length of time DP thymocytes survive in the absence of selection.
已证明bclx基因在体外可调节程序性细胞死亡。我们现在发现，当T细胞从CD4-CD8-（双阴性）胸腺细胞分化为CD4+CD8+[双阳性（DP）]胸腺细胞时，Bclx的表达会显著增加。相比之下，单阳性（SP）胸腺细胞表达的Bclx蛋白量可忽略不计。这种表达模式与Bcl2相反，Bcl2存在于双阴性胸腺细胞中，在DP胸腺细胞中下调，并在成熟为SP胸腺细胞时再次诱导表达。通过基因靶向消除Bclx会显著缩短DP胸腺细胞的存活时间，但不会缩短SP胸腺细胞或外周SP T细胞的存活时间。这些数据表明，胸腺成熟过程中Bclx的诱导在调节DP胸腺细胞在无选择情况下存活的时间长度方面起着关键作用。
