In vivo switch to IL-10-secreting T regulatory cells in high dose allergen exposure.
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 beta 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.
Meiler
Flurina
F
Swiss Institute of Allergy and Asthma Research, University of Zurich, 7270 Davos, Switzerland.
Zumkehr
Judith
J
Klunker
Sven
S
Rückert
Beate
B
Akdis
Cezmi A
CA
Akdis
Mübeccel
M
D000328:Adult; D000368:Aged; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology; D000818:Animals; D001514:Bee Venoms / Q000008:administration & dosage / Q000276:immunology; D001516:Bees; D016207:Cytokines / Q000097:blood / Q000235:genetics / Q000276:immunology; D005260:Female; D006801:Humans; D007108:Immune Tolerance / Q000502:physiology*; D016753:Interleukin-10 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure; D009790:Occupations; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D011968:Receptors, Histamine / Q000235:genetics / Q000276:immunology; D012621:Seasons; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism
D000485:Allergens; D001514:Bee Venoms; D016207:Cytokines; D011948:Receptors, Antigen, T-Cell; D011968:Receptors, Histamine; D016753:Interleukin-10