EXTRACELLULAR ATP IN LYMPHOCYTE-T ACTIVATION - POSSIBLE ROLE IN EFFECTOR FUNCTIONS
EXTRACELLULAR ATP IN LYMPHOCYTE-T ACTIVATION - POSSIBLE ROLE IN EFFECTOR FUNCTIONS
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DOI：
10.1073/pnas.87.21.8267
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发表时间：
1990-11-01
影响因子：
11.1
通讯作者：
SITKOVSKY, MV
中科院分区：
文献类型：
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作者：
FILIPPINI, A;TAFFS, RE;SITKOVSKY, MV
我们假设溶细胞性 T 淋巴细胞 (CTL) 可能在 CTL-靶细胞相互作用的效应器阶段利用细胞外 ATP (ATPo)，并且 CTL 可能是 ATPo 的来源。这里证明，CTL 与激活配体 [Con A 或 T 细胞抗原受体 (TCR) 的单克隆抗体 (mAb)] 一起孵育会导致 ATP/o 不依赖于细胞外 Ca2+ 积累。将 ATP 降解酶添加到 CTL 和靶细胞的混合物中，会强烈抑制 CTL 介导的、TCR 触发的致死攻击向靶细胞的传递。在平行对照实验中，所使用的酶不影响靶细胞诱导的、TCR 触发的 CTL 颗粒的胞吐作用。因此，用酶去除ATPo不会干扰靶细胞对CTL的激活，但会阻止裂解事件。克隆的辅助 T 淋巴细胞在与抗 TCR mAb 或 Con A 孵育后也会积累 ATPo，这表明与胞外蛋白激酶和/或嘌呤能受体协同作用的 ATPo 可能普遍用作 T 淋巴细胞细胞相互作用中的信使。
We hypothesized that cytolytic T lymphocytes (CTL) may utilize extracellular ATP (ATPo) during the effector phase of the CTL-target cell interactions and that CTL could be the source of ATPo. It is demonstrated here that incubation of CTL with activating ligands [Con A or monoclonal antibody (mAb) to the T-cell antigen receptor (TCR)] results in the extracellular Ca2+-independent accumulation of the ATP/o. The addition of the ATP-degrading enzymes into the mixture of CTL and target cells results in a strong inhibition of the CTL-mediated, TCR-triggered lethal-hit delivery to the target cell. In a parallel control experiment, the employed enzymes did not affect target cell-induced, TCR-trigggered exocytosis of granules from CTL. Thus, the removal of ATPo with enzymes does not interfere with the activation of CTL by the target cell but does block lytic events. Cloned helper T lymphocytes also accumulate ATPo after incubation with anti-TCR mAb or Con A, suggesting the possibility that ATPo, which acts in concert with ectoprotein kinase and/or purinergic receptors, may be of general use as a messenger in cellular interactions of T lymphocytes.