Pharmacologic effects of autacoids on subsets of T cells. Regulation of expression/function of histamine-2 receptors by a subset of suppressor cells.
Pharmacologic effects of autacoids on subsets of T cells. Regulation of expression/function of histamine-2 receptors by a subset of suppressor cells.
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自体激素对 T 细胞亚群的药理作用。
DOI：
10.1172/jci111863
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发表时间：
1985
期刊：
影响因子：
--
通讯作者：
Melmon,KL
中科院分区：
文献类型：
--
作者：
Khan,MM;Sansoni,P;Engleman,EG;Melmon,KL
Autacoids（主要是组胺，β肾上腺素能儿茶酚胺，和Escherlandin E和A）最近才被认为是许多免疫功能的实质性调节剂。如果autacoids被认为是潜在的治疗性免疫调节剂，有必要了解它们对T细胞亚群的影响，而它们彼此接触和不接触。这份报告表明，autacoid受体是非随机分布在人类T细胞的表型和功能不同的子集。每个人T细胞亚群对组胺和异丙肾上腺素都有反应，但剂量反应曲线和最大功效在亚群之间变化很大。抑制性T细胞对组胺和异丙肾上腺素的反应性高于辅助/诱导性T细胞（TH）或细胞毒性T细胞（Tc）。我们发现，在促有丝分裂刺激后，对组胺的反应，而不是异丙肾上腺素，大大增加，只有在TH（Leu 3+）和Tc（Leu 2+，9.3+）亚群，这种效果可能是由抑制性T细胞（Leu 2+，9.3-）调节。cAMP积累的显着上升，组胺在有丝分裂原处理的TH和Tc完全阻断H2拮抗剂（西咪替丁），但不是由H1拮抗剂（美托咪定）。这些发现表明相互依赖的（a）免疫未承诺的子集在其响应选定的药物，和（B）控制基础和autacoid诱导的cAMP的生产，以及（c）增加定性和定量的选择性，这是由有丝分裂原。如果我们只在未分离的细胞上进行这些实验，我们就不会观察到自体毒素对T细胞亚群的显著选择性作用。
Autacoids (principally histamine, beta adrenergic catecholamines, and prostaglandins E and A) have only recently been recognized as substantive moderators of a number of immune functions. If autacoids are to be considered as potential therapeutic immunomodulators, it is necessary to understand their effects on subsets of T cells while they are and are not in contact with each other. This report demonstrates that autacoid receptors are nonrandomly distributed on phenotypically and functionally distinct subsets of human T cells. Each human T cell subset responded to both histamine and isoproterenol, but the dose response curve and maximal efficacy varied widely between the subsets. The suppressor T cells were more responsive to both histamine and isoproterenol than helper/inducer T cells (TH) or cytotoxic T cells (Tc). We found that after mitogenic stimulation the response to histamine, but not isoproterenol, was greatly increased only in TH (Leu 3+) and Tc (Leu 2+, 9.3+) subsets, and that this effect may be regulated by suppressor T cells (Leu 2+, 9.3-). The dramatic rise in cAMP accumulation in response to histamine in mitogen-treated TH and Tc was totally blocked by an H2 antagonist (cimetidine), but not by an H1 antagonist (mepyramine). These findings indicate interdependence of (a) immunologically uncommitted subsets in their response to selected drugs, and (b) control of basal- and autacoid-induced cAMP production, as well as (c) increased qualitative and quantitative selectivity, which is caused by mitogen. If we had performed these experiments only on unseparated cells we would not have observed the remarkable selectivity of autacoid effects on subsets of T cells.