Fas (CD95) expression and death-mediating function are induced by CD4 cross-linking on CD4+ T cells.
Fas (CD95) expression and death-mediating function are induced by CD4 cross-linking on CD4+ T cells.
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Fas (CD95) 表达和死亡介导功能是由 CD4 T 细胞上的 CD4 交联诱导的。
DOI：
10.1073/pnas.93.20.11014
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发表时间：
1996
影响因子：
11.1
通讯作者：
Newell,MK
中科院分区：
文献类型：
--
作者：
Desbarats,J;Freed,JH;Campbell,PA;Newell,MK
CD4 受体通过将抗原呈递细胞上的主要组织相容性复合物 II 类与 T 细胞受体 (TCR)/CD3 复合物结合，并触发一系列信号事件（包括细胞内蛋白质的酪氨酸磷酸化）来促进 T 细胞激活。矛盾的是，TCR 刺激之前的 CD3 交联会导致细胞凋亡，就像通过 HIV 糖蛋白 (gp) 120 在 CD4 连接体内注射抗 CD4 抗体一样。在本报告中，我们研究了 CD4 交联诱导细胞死亡的机制。我们发现 CD4 交联会导致细胞表面 Fas 水平小幅但快速增加，Fas 是肿瘤坏死因子受体家族的成员，与细胞凋亡和免疫稳态的维持有关。重要的是，CD4 交联触发了 Fas 作为死亡分子的能力。 CD4 交联后，过夜培养的 CD4+ 脾细胞对 Fas 介导的死亡变得敏感。死亡是 Fas 依赖性的，如在不存在板结合的抗 Fas 抗体的情况下细胞存活以及 Fas 缺陷性淋巴增殖 (lpr) 小鼠的细胞中缺乏 CD4 诱导的死亡所证明的那样。我们在此证明 CD4 调节 Fas 诱导 Cd4+ T 细胞死亡的能力。
The CD4 receptor contributes to T-cell activation by coligating major histocompatibility complex class II on antigen presenting cells with the T-cell receptor (TCR)/CD3 complex, and triggering a cascade of signaling events including tyrosine phosphorylation of intracellular proteins. Paradoxically, CD3 cross-linking prior to TCR stimulation results in apoptotic cell death, as does injection of anti-CD4 antibodies in vivo of CD4 ligation by HIV glycoprotein (gp) 120. In this report we investigate the mechanism by which CD4 cross-linking induces cell death. We have found that CD4 cross-linking results in a small but rapid increase in levels of cell surface Fas, a member of the tumor necrosis factor receptor family implicated in apoptotic death and maintenance of immune homeostasis. Importantly, CD4 cross-linking triggered the ability of Fas to function as a death molecule. Subsequent to CD4 cross-linking, CD4+ splenocytes cultured overnight became sensitive to Fas-mediated death. Death was Fas-dependent, as demonstrated by cell survival in the absence of plate-bound anti-Fas antibody, and by the lack of CD4-induced death in cells from Fas-defective lymphoproliferative (lpr) mice. We demonstrate here that CD4 regulates the ability of Fas to induce cell death in Cd4+ T cells.