Assessment of Bet v 1-specific CD4+ T cell responses in allergic and nonallergic individuals using MHC class II peptide tetramers.
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-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.
Van Overtvelt
Laurence
L
Recherche et Développement, Stallergènes SA, Antony, France.
Wambre
Erik
E
Maillère
Bernard
B
von Hofe
Eric
E
Louise
Anne
A
Balazuc
Anne Marie
AM
Bohle
Barbara
B
Ebo
Didier
D
Leboulaire
Christophe
C
Garcia
Gilles
G
Moingeon
Philippe
P
D000485:Allergens / Q000276:immunology*; D000595:Amino Acid Sequence; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D000949:Histocompatibility Antigens Class II / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology*; D010641:Phenotype; D010940:Plant Proteins / Q000276:immunology*
D000485:Allergens; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D010446:Peptide Fragments; D010940:Plant Proteins