Regulation of Bim by TCR signals in CD4/CD8 double-positive thymocytes

被引:24
作者
Bunin, A
Khwaja, FW
Kersh, GJ
机构
[1] Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA
[2] Emory Univ, Sch Med, Dept Neurosurg, Atlanta, GA 30322 USA
关键词
D O I
10.4049/jimmunol.175.3.1532
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Bim, a B113-only Bcl-2 family member, is required for apoptosis of thymocytes in response to negative selection signals. Regulation of the apoptotic activity of Bim during negative selection is not understood. In this study we demonstrate that in murine thymocytes undergoing apoptosis in response to anti-CD3 epsilon injection, levels of Bim protein expression do not change. In immature thymocytes, Bim is associated with mitochondria before stimulation and is not regulated by a change in subcellular localization during apoptosis. We also show that Bim,, is rapidly phosphorylated in thymocytes in response to ME cross-linking both in vivo and in vitro, and that phosphorylation is sustained for at least 24 h. Analysis of MHC-deficient mice shows that phosphorylation of Bim occurs in CD4/CD8 double-positive thymocytes and does not depend on activation of mature T cells. We also find that TCR cross-linking on thymocytes induces an increase in the proportion of Bel-x(L) bound to Bim at late time points. Our results favor a model in which strong TCR signals regulate the apoptotic activity of Bim by phosphorylation and subsequent changes in binding to Bcl-x(L) in immature thymocytes.
引用
收藏
页码:1532 / 1539
页数:8
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