Histamine regulates T-cell and antibody responses by differential expression of H1 and H2 receptors

Many pathological processes, including those causing allergies and autoimmu ne diseases, are associated with the presence of specialized subsets of T h elper cells (T(H)1 and T(H)2) at the site of inflammation(1-4). The diversi ty of T(H)1 and T(H)2 function is not predetermined but depends on signals that drive the cells towards either subset(1-4). Histamine, released from e ffector cells (mast cells and basophils) during inflammatory reactions can influence immune response(5-8). Here we report that histamine enhances T(H) 1-type responses by triggering the histamine receptor type 1 (H1R), whereas both T(H)1- and T(H)2-type responses are negatively regulated by H2R throu gh the activation of different biochemical intracellular signals. In mice, deletion of H1R results in suppression of interferon (IFN)-gamma and domina nt secretion of T(H)2 cytokines (interleukin (IL)-4 and IL-13). Mutant mice lacking H2R showed upregulation of both T(H)1 and T(H)2 cytokines. Relevan t to T-cell cytokine profiles, mice lacking H1R displayed increased specifi c antibody response with increased immunoglobulin-e (IgE) and IgG1, IgG2b a nd IgG3 compared with mice lacking H2R. These findings account for an impor tant regulatory mechanism in the control of inflammatory functions through effector-cell-derived histamine.