T-cell suppression and contrasuppression induced by histamine H2 and H1 receptor agonists, respectively.
T-cell suppression and contrasuppression induced by histamine H2 and H1 receptor agonists, respectively.
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DOI：
10.1073/pnas.79.16.5052
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发表时间：
1982-08
影响因子：
11.1
通讯作者：
J. Siegel;A. Schwartz;P. Askenase;R. Gershon
中科院分区：
文献类型：
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作者：
J. Siegel;A. Schwartz;P. Askenase;R. Gershon
Lyl+T辅助细胞和延迟型超敏效应细胞活性的强度部分由两类免疫调节性T细胞：抑制细胞和对抗抑制细胞之间的相互作用所控制。我们问组胺，在我们计算的浓度和暴露时间下，是否可以在局部炎症部位达到，可以在体外激活这两类调节细胞中的一种或两种。为了回答这个问题，我们在体内用耐受性原三硝基苯磺酸处理的小鼠脾脏细胞作为体外产生初级抗三硝基苯自身细胞毒性T淋巴细胞的调节剂。在所使用的条件下，这些脾细胞没有主要的调节作用。然而，如果将这些细胞与0.1 mM的组胺预孵育30-60分钟，则会诱导抑制活性，但这种情况不一致，并且具有非化学计量学结果。合成组胺激动剂的使用表明，组胺可以激活抑制细胞亚群和对抗抑制细胞亚群。组胺H1受体激动剂[2-（2-吡啶基）-盐酸乙胺]倾向于激活对照抑制，而H2受体激动剂（地马普利）倾向于激活抑制细胞。因此，组胺可能具有抑制作用的相反作用。这种双重性是通过用补体和抗i- j抗体治疗吡啶乙胺诱导的抗压细胞来证明的，这种抗体可以杀死抗压细胞。这种治疗显示出高水平的抑制细胞活性，直到相反的对抗抑制细胞被移除才表达。由于组胺在延迟型超敏反应的局部部位释放，这些结果表明，组胺可能作为微环境免疫调节的诱导剂，在免疫反应发生的部位激活调节性T细胞。
The intensity of Lyl+T helper and delayed type hypersensitivity effector cell activities is governed, in part, by an interplay between two classes of immunoregulatory T cells: suppressor cells and contrasuppressor cells. We asked whether histamine, at concentrations and duration of exposure that we calculated might be achieved at local sites of inflammation, could activate either or both of these classes of regulatory cells in vitro. To answer this question we used spleen cells from mice treated in vivo with the toleragen trinitrobenzenesulfonic acid as regulators of in vitro generation of primary anti-trinitrophenyl self-cytotoxic T lymphocytes. Under the conditions used, these spleen cells had no major regulatory effects. However, if these cells were preincubated with histamine at 0.1 mM for 30-60 min, suppressor activity was induced, but this occurred inconsistently and with nonstoichiometric results. The use of synthetic histamine agonists revealed that histamine may activate both suppressor and contrasuppressor cell subsets. A histamine H1 receptor agonist [2-(2-pyridyl)-ethylamine dihydrochloride] had a propensity to activate contrasuppression, whereas an H2 receptor agonist (dimaprit) tended to activate suppressor cells. Thus, histamine may have opposing actions that obscure suppression. This duality was shown by treatment of pyridylethylamine-induced contrasuppressor cells with complement and anti-I-J antibody that kills contrasuppressor cells. This treatment revealed a high level of suppressor cell activity that was not expressed until the opposing contrasuppressor cells were removed. Because histamine is released at local sites of delayed type hypersensitivity, these results indicate that histamine may serve as an inducer of microenvironmental immunomodulation by activating regulatory T cells at sites where immune responses are taking place.