Apoptosis regulators Fas and Bim cooperate in shutdown of chronic immune responses and prevention of autoimmunity.
Apoptosis regulators Fas and Bim cooperate in shutdown of chronic immune responses and prevention of autoimmunity.
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DOI：
10.1016/j.immuni.2007.12.017
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发表时间：
2008-02
期刊：
影响因子：
32.4
通讯作者：
Bouillet, Philippe
中科院分区：
文献类型：
--
作者：
Hughes, Peter D.;Belz, Gabrielle T.;Fortner, Karen A.;Budd, Ralph C.;Strasser, Andreas;Bouillet, Philippe
T淋巴细胞的凋亡性死亡对于免疫应答和造血细胞稳态的关闭至关重要。死亡受体（Fas）激活和由仅BH 3蛋白Bim触发的线粒体凋亡都与抗原刺激的T细胞的杀伤有关。我们检查了缺乏Bim（Bcl 2l 11）编码基因和Fas（Fas）编码基因中存在失活lpr突变的小鼠，命名为Bcl 2l 11 −/−Faslpr/lpr小鼠。对单纯疱疹病毒的急性T细胞应答的抑制仅涉及Bim，Fas没有贡献，而在小鼠γ-疱疹病毒慢性感染中，两种途径协同杀死抗原刺激的T细胞。与仅缺乏这些凋亡诱导剂之一的小鼠相比，Bcl 2l 11 −/−Faslpr/lpr小鼠发生了显著增强和加速的致命性淋巴结病和自身免疫。这些结果确定了Fas和Bim在免疫应答关闭和预防免疫病理学中T细胞死亡中的关键重叠作用，从而解决了长期存在的争议。
Apoptotic death of T lymphocytes is critical for shutdown of immune responses and hemopoietic cell homeostasis. Both death receptor (Fas) activation and mitochondrial apoptosis triggered by the BH3-only protein Bim have been implicated in the killing of antigen-stimulated T cells. We examined mice lacking the gene encoding Bim (Bcl2l11) and with the inactivating lpr mutation in the gene encoding Fas (Fas), designated Bcl2l11−/−Faslpr/lpr mice. Shutdown of an acute T cell response to herpes simplex virus involved only Bim with no contribution by Fas, whereas both pathways synergized in killing antigen-stimulated T cells in chronic infection with murine γ-herpesvirus. Bcl2l11−/−Faslpr/lpr mice developed remarkably enhanced and accelerated fatal lymphadenopathy and autoimmunity compared to mice lacking only one of these apoptosis inducers. These results identify critical overlapping roles for Fas and Bim in T cell death in immune response shutdown and prevention of immunopathology and thereby resolve a long-standing controversy.
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影响因子：
56.9
作者：
Opferman, JT;Iwasaki, H;Korsmeyer, SJ
通讯作者：
Korsmeyer, SJ
DOI：
10.1073/pnas.2336198100
发表时间：
2003-11-25
影响因子：
11.1
作者：
Pellegrini, M;Belz, G;Strasser, A
通讯作者：
Strasser, A
影响因子：
5.4
作者：
Grayson, Jason M.;Weant, Ashley E.;Hildeman, David
通讯作者：
Hildeman, David
影响因子：
15.3
作者：
Enders, A;Bouillet, P;Puthalakath, H;Xu, YK;Tarlinton, DM;Strasser, A
通讯作者：
Strasser, A
影响因子：
64.5
作者：
Puthalakath, Hamsa;O'Reilly, Lorraine A.;Strasser, Andreas
通讯作者：
Strasser, Andreas