Intestinal Mucosal Lymphocytes Have H1 Receptors: H1 Antagonists Reduce Their Proliferation and Cytotoxicity

Histamine and H1 antagonists inhibit the proliferation and natural killer activity of peripheral blood mononuclear cells, which express large numbers of H1 receptors. This study examined the presence of H1 receptors and the effects of histamine, H1 antagonists (pyrilamine and diphenhydramine), and H2 antagonists (cimetidine and ranitidine) on human intestinal lymphocyte proliferation and cytotoxicity. Intestinal lymphocytes were obtained by chemical and enzymatic treatment of surgical specimens and purified by Percoll density gradient centrifugation. Proliferation was measured by [3H]thymidine incorporation of mitogen-stimulated lymphocytes; cytotoxicity was measured by the standard 51 Cr-release assay using HT-29 adenocarcinoma target cells. Scatchard analysis of radioligand binding using [3H]pyrilamine demonstrated H1 receptors. The mitogen-induced proliferative responses of intraepithelial lymphocytes and lamina propria lymphocytes were inhibited by histamine and the H1 antagonists but not the H2 antagonists. Cytotoxic activities of fresh or IL-2-stimulated mucosal lymphocytes (spontaneous and lymphokine-activated killing, respectively) were also reduced by the H1 antagonists. A large number of H1 receptors were found on intraepithelial lymphocytes and peripheral blood mononuclear cells and still more on lamina propria lymphocytes. Intestinal lymphocytes bear H1 receptors; histamine and H1 antagonists have immunomodulatory effects on these cells.