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

We report that histamine enhances TH1-type responses by triggering the histamine receptor type 1, whereas both TH1- and TH2-type responses are negatively regulated by H2R through the activation of different biochemical intracellular signals

Marek Jutel

2002

Scholarcy highlights

  • Many pathological processes, including those causing allergies and autoimmune diseases, are associated with the presence of specialized subsets of T helper cells at the site of inflammation
  • We investigated the expression of these receptors on TH1 and TH2 cells bearing the CD4 antigen and whether histamine stimulation exerts differential effects on these cells
  • Cells bearing the histamine receptor were stained with fluorescein-labelled histamine; histamine bound significantly more strongly to TH1 cells than to TH2 cells
  • These results demonstrate that CD45RO+ TH1 and TH2 cells preferentially but not exclusively express H1R and H2R, respectively, and that H1R and H2R are regulated by cytokines present in the immune environment
  • Only TH2 cells showed dose-dependent increases in cAMP to histamine stimulation. This effect was fully abrogated by the specific H2R antagonist ranitidine but not by tripelennamine, indicating the H2R-dominated signalling in TH2 cells
  • The concentrations of tripelennamine, ranitidine and clobenpropit were 1,000 times the pA2 value, that is, the negative logarithm of the concentration required to get 50% reduction of the efficacy of histamine
  • We further investigated whether distinct intracellular events induced in TH1 and TH2 cells on stimulation with histamine influence the functions of immune effectors
  • Serum was collected at day 28 and OVA-specific IgG1, IgG2a, IgG2b and IgG3 were determined in serial dilutions in duplicates by ELISA8

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