The Journal of Experimental Medicine
Rockland Immunochemicals for Research
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Published online November 10, 2008
doi:10.1084/jem.20080193
The Journal of Experimental Medicine, Vol. 205, No. 12, 2887-2898
The Rockefeller University Press, 0022-1007 $30.00
© 2008 Meiler et al.
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ARTICLE

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

Flurina Meiler, Judith Zumkehr, Sven Klunker, Beate Rückert, Cezmi A. Akdis, and Mübeccel Akdis

Swiss Institute of Allergy and Asthma Research, University of Zurich, 7270 Davos, Switzerland

CORRESPONDENCE Mübeccel Akdis: akdism{at}siaf.unizh.ch

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.

Abbreviations used: CTLA, CTL-associated antigen; HR, histamine receptor; PD, programmed death; PLA, phospholipase A2; PPD, purified protein derivative; SIT, specific immunotherapy; TCRVβ, TCR variable β; Tr1, type 1 T regulatory; TT, tetanus toxoid.

F. Meiler and J. Zumkehr contributed equally to this paper.

© 2008 Meiler et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).


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Related In this Issue article

Beekeepers show way to allergen tolerance
Nicole LeBrasseur
J. Exp. Med. 2008 205: 2689. [Full Text] [PDF]





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