T-cell suppression and contrasuppression induced by histamine H2 and H1 receptor agonists, respectively.

Abstract

The intensity of Ly1+ T helper and delayed type hypersensitivity effector cell activities is governed, in part, by an interplay between 2 classes of immunoregulatory T cells: suppressor cells and contrasuppressor cells. A study was made to determine whether histamine, at concentrations and duration of exposure that might be achieved at local sites of inflammation, could activate either or both of these classes of regulatory cells in vitro. Spleen cells were used 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. 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 might 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. Histamine may have opposing actions that obscure suppression. This duality is 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, histamine may serve as an inducer of microenvironmental immunomodulation by activating requlatory T cells at sites where immune responses are taking place.