HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Van Overtvelt, L. Articles by Moingeon, P. PubMed PubMed Citation Articles by Van Overtvelt, L. Articles by Moingeon, P. Pubmed/NCBI databases Substance via MeSH Medline Plus Health Information Allergy

Assessment of Bet v 1-Specific CD4⁺ T Cell Responses in Allergic and Nonallergic Individuals Using MHC Class II Peptide Tetramers¹

Laurence Van Overtvelt^2,*, Erik Wambre^2,*, Bernard Maillère, Eric von Hofe^||, Anne Louise, Anne Marie Balazuc, Barbara Bohle^#, Didier Ebo^**, Christophe Leboulaire, Gilles Garcia^¶ and Philippe Moingeon^3,*

^* Recherche et Développement, Stallergènes SA, Antony; Service d’Ingénierie Moléculaire des Protéines, Commissariat à l’Energie Atomique, Gif sur Yvette; Institut Pasteur, Paris; Beckman Coulter, Marseille; ^¶ Département de Pneumologie, Hôpital Béclère, Clamart, France; ^|| Antigen Express, Worcester, MA 01605; ^# Department of Pathophysiology, Medical University of Vienna, Vienna, Austria; and ^** Department of Immunology, Allergy and Rheumatology, Antwerp University, Antwerp, Belgium

In this study, we used HLA-DRB1*0101, DRB1*0401, and DRB1*1501 peptide tetramers combined with cytokine surface capture assays to characterize CD4⁺ T cell responses against the immunodominant T cell epitope (peptide 141–155) from the major birch pollen allergen Bet v 1, in both healthy and allergic individuals. We could detect Bet v 1-specific T cells in the PBMC of 20 birch pollen allergic patients, but also in 9 of 9 healthy individuals tested. Analysis at a single-cell level revealed that allergen-specific CD4⁺ T cells from healthy individuals secrete IFN- and IL-10 in response to the allergen, whereas cells from allergic patients are bona fide Th2 cells (producing mostly IL-5, some IL-10, but no IFN-), as corroborated by patterns of cytokines produced by T cell clones. A fraction of Bet v 1-specific cells isolated from healthy, but not allergic, individuals also expresses CTLA-4, glucocorticoid-induced TNF receptor, and Foxp 3, indicating that they represent regulatory T cells. In this model of seasonal exposure to allergen, we also demonstrate the tremendous dynamics of T cell responses in both allergic and nonallergic individuals during the peak pollen season, with an expansion of Bet v 1-specific precursors from 10^–6 to 10^–3 among circulating CD4⁺ T lymphocytes. Allergy vaccines should be designed to recapitulate such naturally protective Th1/regulatory T cell responses observed in healthy individuals.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was founded by the Fonds zur Förderung der wissenschaftlichen Forschung (SFB-F1807-B04), Austria. E.W. is a recipient of a Convention Industrielle de Formation par la Recherche fellowship from the French government.

² L.V.O. and E.W. contributed equally to this work.

³ Address correspondence and reprint requests to Dr. Philippe Moingeon, Stallergènes, 6 rue Alexis de Tocqueville, 92183 Antony, France. E-mail address: pmoingeon{at}stallergenes.fr

⁴ Abbreviations used in this paper: BP, birch pollen; DC, dendritic cell; ECD, PE-Texas red; GITR, glucocorticoid-induced TNF receptor; HDM, house dust mite; Ii, invariant chain; PC7, phycoerythrin-cyanine 7, PC7; rBet v 1, recombinant Bet v 1; TCC, T cell clone; Treg, regulatory T.