Activation of p38 mitogen-activated protein kinase in vivo selectively induces apoptosis of CD8<SUP>+</SUP> but not CD4<SUP>+</SUP> T cells

作     者：Merritt, C Enslen, H Diehl, N Conze, D Davis, RJ Rincón, M 

作者机构：Univ Vermont Dept Med Immunobiol Program Burlington VT 05405 USA Univ Massachusetts Sch Med Dept Biochem & Mol Biol Program Mol Med Worcester MA 01605 USA Howard Hughes Med Inst Worcester MA 01605 USA 

出 版 物：《MOLECULAR AND CELLULAR BIOLOGY》 (分子生物学与细胞生物学)

年 卷 期：2000年第20卷第3期

页      面：936-946页

核心收录：

学科分类：0710[理学-生物学] 071010[理学-生物化学与分子生物学] 07[理学] 

基　　金：NCI NIH HHS [R01 CA065861  CA 65861  P01 CA072009  CA7209] Funding Source: Medline 

主　　题：细胞凋亡/生理学 CD4阳性T淋巴细胞/细胞学 CD4阳性T淋巴细胞/免疫学 CD4阳性T淋巴细胞/生理学 CD8阳性T淋巴细胞/细胞学 CD8阳性T淋巴细胞/免疫学 CD8阳性T淋巴细胞/生理学 钙-钙调素依赖性蛋白激酶类 细胞 培养的 酶激活 流式细胞术 基因表达调控 淋巴结/免疫学 淋巴细胞活化 MAP激酶激酶6 小鼠 转基因 丝裂原激活蛋白激酶激酶类/遗传学 丝裂原激活蛋白激酶激酶类/代谢 丝裂原激活蛋白激酶类/代谢 原癌基因蛋白质c-bcl-2/遗传学 逆转录聚合酶链反应 脾/免疫学 p38丝裂原活化蛋白激酶类 动物 小鼠 

摘      要：CD4(+) and CD8(+) T cells play specific roles during an immune response. Different molecular mechanisms could regulate the proliferation, death, and effector functions of these two subsets of T cells. The p38 mitogen-activated protein (MAP) kinase pathway is induced by cytokines and environmental stress and has been associated with cell death and cytokine expression. Here me report that activation of the p38 MAP kinase pathway in vivo causes a selective loss of CD8(+) T cells due to the induction of apoptosis. In contrast, activation of p38 MAP kinase does not induce CD4(+) T-cell death. The apoptosis of CD8(+) T cells is associated with decreased expression of the antiapoptotic protein Bcl-2. Regulation of the p38 MAP kinase pathway in T cells is therefore essential for the maintenance of CD4/CD8 homeostasis in the peripheral immune system. Unlike cell death, gamma interferon production is regulated by the p38 MAP kinase pathway in bath CD4(+) and CD8(+) T cells, Thus, specific aspects of CD4(+) and CD8(+) T-cell function are differentially controlled by the p38 MAP kinase signaling pathway.