Interleukin-4 differentially regulates interleukin-2-mediated and CD2-mediated induction of human lymphokine-activated killer effectors.
Interleukin-4 differentially regulates interleukin-2-mediated and CD2-mediated induction of human lymphokine-activated killer effectors.
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Interleukin-4 差异性地调节 IL-2 介导和 CD2 介导的人淋巴因子激活杀伤效应器的诱导。
DOI：
10.1002/eji.1830221116
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发表时间：
1992
影响因子：
5.4
通讯作者：
Chouaib,S
中科院分区：
文献类型：
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作者：
Robinet,E;Kamoun,M;Farace,F;Chouaib,S
自然杀伤（NK）细胞可以在白细胞介素（IL）-2刺激后分化为淋巴因子激活的杀伤（LAK）效应细胞。这种诱导可以通过IL-4负调控。在这项研究中，我们证明了通过CD 2途径用（9 - 1 + 9.6）单克隆抗体刺激NK细胞也可以诱导这些细胞分泌肿瘤坏死因子-α（TNF-α）并分化为LAK效应子。更重要的是，我们的数据表明，与IL-2诱导的LAK生成相反，抗CD 2触发的LAK活性不受IL-4的调节。发现IL-4可增强LAK活性以及抗CD 2激活后的NK细胞增殖，其机制至少部分涉及TNF-α产生增加。使用针对Fc受体的固定化单克隆抗体我们还观察到抗CD 16诱导的LAK活性不受IL-4的抑制。这些数据进一步表明TNF-α作为一种调节细胞因子在抗CD 2诱导的LAK产生中起着关键作用，并表明IL-4可以作为参与非MHC限制性T细胞活化的两种不同途径之间的区分因子。细胞毒
Natural killer (NK) cells can be differentiated into lymphokine‐activated killer (LAK) effectors following stimulation with interleukin (IL)‐2. This induction can be negatively regulated by IL‐4. In this study, we demonstrate that the stimulation of NK cells through the CD2 pathway with (9‐1 + 9.6) monoclonal antibodies can also induce these cells to secrete tumor necrosis factor‐α (TNF‐α) and to differentiate into LAK effectors. More importantly, our data indicate that, in contrast to the IL‐2‐induced LAK generation, the anti‐CD2‐triggered LAK activity was not regulated by IL‐4. IL‐4 was found to enhance the LAK activity as well as NK cell proliferation following activation with anti‐CD2 by a mechanism involving, at least in part, an increased TNF‐α production. Using immobilized monoclonal antibodies against the Fc receptor (FcγRIII or CD16) for NK stimulation, we also observed that the anti‐CD16‐induced LAK activity was not inhibited by IL‐4.These data further point to a pivotal role of TNF‐α as a regulatory cytokine in anti‐CD2‐induced LAK generation, and suggest that IL‐4 could serve as a discriminatory factor between two distinct pathways involved in the activation of non‐MHC‐restricted cytotoxicity.