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

• Published in: The Journal of experimental medicine Vol. 205; no. 12; pp. 2887 - 2898
• Main Authors: Meiler, Flurina, Zumkehr, Judith, Klunker, Sven, Rückert, Beate, Akdis, Cezmi A., Akdis, Mübeccel
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 24.11.2008
• Subjects: Adult; Aged; Allergens - administration & dosage; Allergens - immunology; Animals; Bee Venoms - administration & dosage; Bee Venoms - immunology; Bees; Cytokines - blood; Cytokines - genetics; Cytokines - immunology; Female; Humans; Immune Tolerance - physiology; Interleukin-10 - secretion; Male; Middle Aged; Occupational Exposure; Occupations; Receptors, Antigen, T-Cell - genetics; Receptors, Antigen, T-Cell - immunology; Receptors, Histamine - genetics; Receptors, Histamine - immunology; Seasons; T-Lymphocyte Subsets - immunology; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - secretion
• ISSN: 0022-1007; 1540-9538; 1540-9538
• DOI: 10.1084/jem.20080193

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.