期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1982
卷号：79
期号：16
页码：5052-5056
DOI：10.1073/pnas.79.16.5052
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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.
