Histamine type 2 receptor expression on peripheral blood regulatory lymphocytes in patients with allergic rhinitis treated with specific immunotherapy

Background: Both histamine H1- and H2-receptors (H2R) were found on regulatory T (Treg) cells; however, there is a paucity of information regarding the role of H2R in Treg function. This study aimed to investigate the effects of natural allergen stimulation and specific immunotherapy (SIT) on H2R expression in Treg cells in patients with allergic rhinitis (AR). Methods: In this prospective, double-blind, placebo-controlled study 41 patients with AR were screened for 1 year and treated with SIT (n = 21) or placebo (n = 20) for the next 2 years. Fifteen healthy subjects were included as a control. Subsets of Treg cells that expressed H2R were assessed annually in the blood by flow cytometry: before, at the height of the pollen season, and after, at the end of the pollen season. In addition, total nasal symptom score, the use of rescue medication, and nasal eosinophilia were evaluated. Results: Treg cells of AR patients slightly up-regulate H2R out of the pollen season. Natural allergen stimulation results in prompt up-regulation of H2R within these cells. SIT significantly decreased the number of Treg cells with increased expression of H2R in the blood exclusively at the height of pollen season, which, however, had no impact on the expression of H2R in Treg cells. SIT improved significantly the symptom score, rescue medication use, and decreased nasal eosinophilia. Conclusion: Natural pollen exposure results in up-regulation of H2R in Treg cells. Immunotherapy might transiently decrease the number of Treg-H2R(+) cells in the blood, which may be associated with their migration to the peripheral tissues.