Inhibitory Effects of Histamine on Interleukin 2 and Gamma Interferon Production by Different Human T Helper Cell Subsets

We have previously demonstrated that histamine can inhibit human helper T cells by direct interaction with these cells. It has now been investigated whether histamine inhibits lymphokine production by various subsets of CD4+ human T cells separated with the Leu‐8 (p80) and Leu‐18 (anti‐CD45R; p220) monoclonal antibodies (MoAb). Histamine was shown to suppress to a similar extent the production of interleukin 2 (IL‐2) and gamma interferon (IFN‐γ) by Leu 3+, Leu 3+8+, and Leu 3+8− cell subsets. Mitogen‐activated, unseparated Leu 3+ and purified Leu 3+8− cells produced maximal amounts of IL‐2 after 24 h and IFN‐γ after 72 h of culture. In contrast, the Leu 3+18+ subset produced no IL‐2 after 24 h, and maximal amounts of IL‐2 no sooner than 48 h of culture, and only small amounts of IFN‐γ during the entire culture period of 96 h. Histamine suppressed the production of IL‐2 by both subsets, both when produced early (after 24 h), as in the case of the Leu 3+18− subset, and late (after 48 h of culture), as for the Leu 3+18+subset. The IFN‐γ production by the Leu 3+ and Leu 3+18−cells and the marginal production by Leu 3+18+ cells were significantly suppressed by histamine. Dual staining with Leu 8 and Leu 18 MoAb demonstrated that the Leu 18− cell compartment included both Leu 8+ and Leu 8− cells. It was shown that the inhibitory effect of histamine on the early production of IL‐2 and the major production of IFN‐γ by T helper cells is mediated via action on both the Leu 3+18−8− and the Leu 3+18−8+ cells. The inhibitory effect of histamine on the late production of IL‐2 is mediated mainly via action on Leu‐18+ cells.