Assessment of Bet v 1-specific CD4+ T cell responses in allergic and nonallergic individuals using MHC class II peptide tetramers

被引:101
|
作者
Van Overtvelt, Laurence [1 ]
Wambre, Erik [1 ]
Maillere, Bernard [2 ]
von Hofe, Eric [6 ]
Louise, Anne [3 ]
Balazuc, Anne Marie [3 ]
Bohle, Barbara [7 ]
Ebo, Didier [8 ]
Leboulaire, Christophe [4 ]
Garcia, Gilles [5 ]
Moingeon, Philippe [1 ]
机构
[1] Stallergenes SA, Rech & Dev, F-92183 Antony, France
[2] Commissariat Energie Atom, Serv Ingn Mol Prot, Gif Sur Yvette, France
[3] Inst Pasteur, Paris, France
[4] Beckman Coulter, Marseille, France
[5] Hop Antoine Beclere, Dept Pneumol, Clamart, France
[6] Antigen Express, Worcester, MA 01605 USA
[7] Med Univ Vienna, Dept Pathophysiol, Vienna, Austria
[8] Univ Antwerp, Dept Immunol Allergy & Rheumatology, Antwerp, Belgium
来源
JOURNAL OF IMMUNOLOGY | 2008年 / 180卷 / 07期
关键词
D O I
10.4049/jimmunol.180.7.4514
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
In this study, we used HLA-DRB1*0101, DRB1*0401, and DRBI*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 I-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-gamma 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-gamma), 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.
引用
收藏
页码:4514 / 4522
页数:9
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