FAS AND ITS LIGAND IN A GENERAL MECHANISM OF T-CELL-MEDIATED CYTOTOXICITY
FAS AND ITS LIGAND IN A GENERAL MECHANISM OF T-CELL-MEDIATED CYTOTOXICITY
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DOI：
10.1073/pnas.91.11.4930
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发表时间：
1994-05-24
影响因子：
11.1
通讯作者：
OKUMURA, K
中科院分区：
文献类型：
--
作者：
HANABUCHI, S;KOYANAGI, M;OKUMURA, K
为了探讨T细胞介导的细胞毒作用的机制，我们估计了诱导凋亡的Fas分子在靶细胞上的参与及其配体在效应细胞上的参与。当用ConA或抗CD 3单克隆抗体重定向时，CD 4（+）T细胞克隆BK 1能裂解表达野生型Fas分子的靶细胞，但不能裂解表达死亡信号缺陷型突变体的靶细胞。这表明Fas介导的信号转导参与了BK 1对靶细胞的裂解。抗CD 3激活的非静息状态的蝙蝠BK 1通过可溶性Fas Ig融合蛋白的结合检测到Fas配体的表达，并且BK 1介导的细胞毒性被添加Fas Ig阻断，暗示诱导型Fas配体在BK 1的细胞毒性中。发挥Fas介导的细胞毒性的能力不限于BK 1，但脾CD 4（+）T细胞和在较小程度上，CD 8（+）T细胞也可以发挥Fas依赖的靶细胞裂解。这表明Fas介导的靶细胞溶解途径通常参与T细胞介导的细胞毒性。有趣的是，从gld/gld小鼠制备的CD 4（+）T细胞不介导Fas介导的细胞毒性，表明功能性Fas配体在gld小鼠中的表达缺陷。
To investigate the mechanisms of T-cell-mediated cytotoxicity, we estimated the involvement of apoptosis-inducing Fas molecule on the target cells and its ligand on the effector cells. When redirected by ConA or anti-CD3 monoclonal antibody, a CD4(+) T-cell clone, BK1, could lyse the target cells expressing wild-type Fas molecule but not those expressing death signaling-deficient mutants. This indicates the involvement of Fas-mediated signal transduction in the target cell lysis by BK1. Anti-CD3-activated bat not resting BK1 expressed Fas ligand as detected by binding of a soluble Fas-Ig fusion protein, and the BK1-mediated cytotoxicity was blocked by the addition of Fas-Ig, implicating the inducible Fas ligand in the BK1 cytotoxicity. Ability to exert the Fas mediated cytotoxicity was not confined to BK1, but splenic CD4(+) T cells and, to a lesser extent, CD8(+) T cells could also exert the Fas-dependent target cell lysis. This indicates that the Fas-mediated target cell lytic pathway fan be generally involved in the T-cell-mediated cytotoxicity. Interestingly, CD4(+) T cells prepared from gld/gld mice did not mediate the Fas-mediated cytotoxicity, indicating defective expression of functional Fas ligand in gld mice.