Fas-mediated cytotoxicity. An immunoeffector or immunoregulatory pathway in T cell-mediated immune responses?

Fas-mediated cytotoxicity. An immunoeffector or immunoregulatory pathway in T cell-mediated immune responses?
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Fas 介导的细胞毒性。

DOI:
10.1097/00007890-199508000-00002
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发表时间:
1995
期刊:
影响因子:
6.2
通讯作者:
Pearson,TC
Pearson,TC
中科院分区:
医学2区
文献类型:
--
作者:
Larsen,CP;Alexander,DZ;Hendrix,R;Ritchie,SC;Pearson,TC

文献摘要

被引文献

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Fas/Fas配体相互作用充当细胞凋亡的信号传导途径(1-3),细胞凋亡是免疫系统发育和功能中的重要调节机制(4-9)。Fas依赖性细胞凋亡也是T细胞细胞毒性的一种重要模式的最近证据(10-13)表明Fas可能在T依赖性免疫应答的效应期(例如同种异体移植物排斥)中起关键作用。我们观察到Fas转录本在同基因和异基因小鼠心脏移植物中组成型表达,而Fas配体(FasL)仅在排斥性同种异体移植物中上调。令人惊讶的是,完整的Fas/FasL通路的缺失并没有改变同种异体移植排斥反应的克里思,甚至是CD 4依赖性排斥反应。这些结果表明Fas/FasL相互作用不是T细胞诱导的同种异体移植物损伤的重要介质。相反,如在其他研究中所提出的,Fas途径可能主要参与免疫应答期间T细胞群体的克隆扩增和随后的收缩的调节。
Fas/Fas ligand interactions serve as a signaling pathway for apoptosis (1–3), an important regulatory mechanism in the development and function of the immune system (4–9). Recent evidence that Fas-dependent apoptosis is also an important mode of T cell cytotoxicity (10–13) suggested that Fas might play a critical role in the effector phase of T-dependent immune responses, such as allograft rejection. We observed that Fas transcripts are constitutively expressed in syngeneic and allogeneic murine cardiac transplants, while Fas ligand (FasL) is up-regulated only in rejecting allografts. Surprisingly, the absence of an intact Fas/FasL pathway did not alter the tempo of allograft rejection, even CD4-dependent rejection. These results indicate that Fas/FasL interactions are not essential mediators of T cell-induced allograft damage. Rather, as suggested in other studies, the Fas pathway may be principally involved in the regulation of clonal expansion and subsequent contraction of T cell populations during immune responses.