Modulation of cellular-immune responses in vivo and in vitro by histamine receptor-bearing lymphocytes.

Histamine, one of the mediators involved in the IgE-mediated reaction, was demonstrated to influence in vivo and in vitro components of cellular-immune reactions in orthochlorbenzoyl-bovine gamma globulin-immune guinea pigs. 10(-3) M histamine reduced by half the size of a delayed hypersensitivity skin test at 24 h. Inhibition of skin reactivity by histamine could be partially reversed by H-1 receptor antagonists such as chlorpheniramine and completely prevented by H-2 receptor antagonists such as burimamide. The histamine suppression of cutaneous delayed hypersensitivity could be accounted for in part by its inhibitory effect on certain lymphocyte responses including antigen-induced migration inhibitory factor (MIF) production and proliferation. At concentrations of 10(-3)-10(-5) M histamine reversibly inhibited MIF production and its action could be blocked by H-2 antagonists but not H-1 antagonists. Thus, lymphocytes bearing H-2 receptors modulate MIF production and probably lymphocyte proliferation as well. Histamine did not interfere with the macrophage response to preformed MIF. These studies indicate that immediate hypersensitivity reactions involving histamine release might influence the subsequent expression of cellular-immune reactions.