Histamine via the histamine H₂-receptor reduces α-CD3-induced interferon-γ synthesis in murine CD4+ T cells in an indirect manner.

Histamine is involved in the execution of an immune reaction. Receptors for histamine, of which four different subtypes are known so far, are found on dendritic cells and on T cells. Via these receptors, histamine either indirectly or directly affects the activation of T cells. Data in the literature regarding the involved receptor subtypes and the mode of action of histamine on T cells are somewhat contradictory and depend on the type of cells analyzed, polarized T cells, or freshly prepared T cells within the context of the whole splenocyte population. Therefore, we analyzed the effect of histamine on murine T cells within splenocytes in a detailed manner. We stimulated freshly prepared splenocytes in the presence or absence of histamine with α-CD3 in vitro and analyzed the induced cytokine production. We show that histamine reduced the α-CD3-induced interferon-γ (IFN-γ) production of CD4⁺ cells via the histamine H₂-receptor. Moreover, the effect of histamine on the α-CD3-induced IFN-γ production could be transferred within conditioned splenocyte supernatants induced by histamine (in the absence of α-CD3). Thus, the histamine effect is mediated by a soluble factor, which, however, is neither of the classical anti-inflammatory mediators, interleukin-10, or transforming growth factor-β.