The death receptor fas (CD95/APO-1) mediates the deletion of T lymphocytes undergoing homeostatic proliferation
The death receptor fas (CD95/APO-1) mediates the deletion of T lymphocytes undergoing homeostatic proliferation
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DOI：
10.4049/jimmunol.175.7.4374
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发表时间：
2005-10-01
影响因子：
4.4
通讯作者：
Budd, RC
中科院分区：
文献类型：
--
作者：
Fortner, KA;Budd, RC
过继转移到同基因淋巴细胞减少受体中的鼠T细胞经历增殖。尽管持续的细胞分裂，这种淋巴细胞减少诱导的或稳态的，有限数量的转移的T细胞的增殖不会填充T细胞区室。即使在达到稳定的T细胞数量之后，转移的T细胞的持续扩增也表明主动细胞死亡阻止了T细胞数量的进一步增加。在这项研究中，我们表明，野生型T细胞进行稳态增殖是敏感的Fas介导的细胞死亡。在不存在Fas的情况下，T细胞在转移到淋巴细胞减少的受体中后积累到显著更高的水平。因此，Fas是在T细胞稳态期间响应于自身肽/MHC的外周T细胞扩增的主要调节因子。由于Fas缺陷型lpr小鼠在胸腺阴性选择或外源性Ag诱导的外周T细胞缺失中未表现出显著异常，因此其淋巴结病可能是由于不受限制的稳态增殖所致。
Murine T cells adoptively transferred into syngeneic lymphopenic recipients undergo proliferation. Despite continued cell division, this lymphopenia-induced or homeostatic, proliferation of a limited number of transferred T cells does not fill the T cell compartment. The continued expansion of the transferred T cells, even after stable T cell numbers have been reached, suggests that active cell death prevents further increase in T cell number. In this study, we show that wild-type T cells undergoing homeostatic proliferation are sensitive to Fas-mediated cell death. In the absence of Fas, T cells accumulate to significantly higher levels after transfer into lymphopenic recipients. Fas is, thus, a principal regulator of the expansion of peripheral T cells in response to self-peptide/MHC during T cell homeostasis. As Fas-deficient lpr mice manifest no significant abnormalities in thymic negative selection or in foreign Ag-induced peripheral T cell deletion, their lymphadenopathy may result from unrestrained homeostatic proliferation.