Apoptosis regulators Fas and Bim synergistically control T-lymphocyte homeostatic proliferation.
Apoptosis regulators Fas and Bim synergistically control T-lymphocyte homeostatic proliferation.
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凋亡调节因子 Fas 和 Bim 协同控制 T 淋巴细胞稳态增殖。
DOI：
10.1002/eji.201040577
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发表时间：
2010-11
影响因子：
5.4
通讯作者：
Budd, Ralph C.
中科院分区：
文献类型：
--
作者：
Fortner, Karen A.;Bouillet, Philippe;Strasser, Andreas;Budd, Ralph C.
外周T淋巴细胞室的大小是由复杂的平衡T细胞增殖和死亡的稳态机制控制的。增殖和存活信号部分由反复出现的自肽/MHC-TCR相互作用和常见的含γ链的细胞因子受体（包括IL-7和IL-15）的信号传导介导。我们之前的研究表明，死亡受体Fas （CD95/APO-1）在反复的TCR刺激下调节细胞凋亡，而BH3-only蛋白Bim介导细胞因子戒断诱导的细胞凋亡。因此，我们推断这两种分子可能协同调节稳态增殖。在这项研究中，我们观察到Fas和Bim的联合缺失协同增强了淋巴细胞减少的宿主小鼠中T细胞的积累，这在Fas缺陷（Faslpr/lpr）小鼠特有的不寻常的CD4 - CD8 - TCRαβ+ T细胞中尤为明显。我们的研究结果表明，这些CD4 - CD8 - TCRαβ+ T细胞起源于CD8+ T细胞的稳态增殖。这些研究还强调了即使在没有外源抗原的情况下，野生型小鼠中可能发生的基线T细胞增殖的深刻速率，以及由此产生的多种死亡信号通路对其协调调节的需求。
The size of the peripheral T lymphocyte compartment is governed by complex homeostatic mechanisms that balance T cell proliferation and death. Proliferation and survival signals are mediated in part by recurrent self-peptide/MHC-TCR interactions and signaling by the common γ chain-containing cytokine receptors, including those for IL-7 and IL-15. We have previously shown that the death receptor Fas (CD95/APO-1) regulates apoptosis in response to repeated TCR stimulation whereas the BH3-only protein Bim mediates cytokine withdrawal-induced apoptosis. We therefore reasoned that these two molecules might cooperate in the regulation of homeostatic proliferation. In this study, we observe that the combined loss of Fas and Bim synergistically enhances the accumulation of T cells in lymphopenic host mice, and this is particularly pronounced for the unusual CD4−CD8−TCRαβ+ T cells that are characteristic of Fas-deficient (Faslpr/lpr) mice. Our findings demonstrate that these CD4−CD8−TCRαβ+ T cells arise from homeostatic proliferation of CD8+ T cells. These studies also underscore the profound rate of baseline T cell proliferation that likely occurs in wild-type mice even in the absence of foreign antigen, and the consequent need for its coordinated regulation by multiple death-signaling pathways.
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影响因子：
32.4
作者：
Ernst, B;Lee, DS;Surh, CD
通讯作者：
Surh, CD
DOI：
10.1084/jem.20021387
发表时间：
2003-02-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Barthlott T;Kassiotis G;Stockinger B
通讯作者：
Stockinger B
影响因子：
32.4
作者：
Hughes, Peter D.;Belz, Gabrielle T.;Fortner, Karen A.;Budd, Ralph C.;Strasser, Andreas;Bouillet, Philippe
通讯作者：
Bouillet, Philippe
影响因子：
4.4
作者：
Fortner, KA;Budd, RC
通讯作者：
Budd, RC
影响因子：
32.4
作者：
Hutcheson, Jack;Scatizzi, John C.;Perlman, Harris
通讯作者：
Perlman, Harris