In vivo switch to IL-10–secreting T regulatory cells in high dose allergen exposure

• DOI: 10.1084/jem.20080193
• Publication Date: 2008-11-11T02:06:55Z
• Authors: Flurina Meiler; Judith Zumkehr; Sven Klunker; Beate Rückert; Cezmi A. Akdis; Mübeccel Akdis
• Keywords: Adult; Male; Receptors, Antigen, T-Cell; 610 Medicine & health; T-Lymphocytes, Regulatory; 03 medical and health sciences; 0302 clinical medicine; 10183 Swiss Institute of Allergy and Asthma Research; T-Lymphocyte Subsets; Occupational Exposure; Immune Tolerance; Animals; Humans; Occupations; Aged; 2403 Immunology; Articles; Allergens; Bees; Middle Aged; Interleukin-10; Bee Venoms; 2723 Immunology and Allergy; Cytokines; Receptors, Histamine; Female; Seasons

High dose bee venom exposure in beekeepers by natural bee stings represents a model to understand mechanisms of T cell tolerance to allergens in healthy individuals. Continuous exposure of nonallergic beekeepers to high doses of bee venom antigens induces diminished T cell–related cutaneous late-phase swelling to bee stings in parallel with suppressed allergen-specific T cell proliferation and T helper type 1 (Th1) and Th2 cytokine secretion. After multiple bee stings, venom antigen–specific Th1 and Th2 cells show a switch toward interleukin (IL) 10–secreting type 1 T regulatory (Tr1) cells. T cell regulation continues as long as antigen exposure persists and returns to initial levels within 2 to 3 mo after bee stings. Histamine receptor 2 up-regulated on specific Th2 cells displays a dual effect by directly suppressing allergen-stimulated T cells and increasing IL-10 production. In addition, cytotoxic T lymphocyte–associated antigen 4 and programmed death 1 play roles in allergen-specific T cell suppression. In contrast to its role in mucosal allergen tolerance, transforming growth factor β does not seem to be an essential player in skin-related allergen tolerance. Thus, rapid switch and expansion of IL-10–producing Tr1 cells and the use of multiple suppressive factors represent essential mechanisms in immune tolerance to a high dose of allergens in nonallergic individuals.