@article{54ecab94a25a42129a65fe0a2d8c6254,
title = "Specific immunotherapy modifies allergen-specific CD4+ T-cell responses in an epitope-dependent manner",
abstract = "Background Understanding the mechanisms by which the immune system induces and controls allergic inflammation at the T-cell epitope level is critical for the design of new allergy vaccine strategies. Objective We sought to characterize allergen-specific T-cell responses linked with allergy or peripheral tolerance and to determine how CD4+ T-cell responses to individual allergen-derived epitopes change over allergen-specific immunotherapy. Methods Timothy grass pollen (TGP) allergy was used as a model for studying grass pollen allergies. The breadth, magnitude, epitope hierarchy, and phenotype of the DR04:01-restricted TGP-specific T-cell responses in 10 subjects with grass pollen allergy, 5 nonatopic subjects, and 6 allergy vaccine-treated subjects was determined by using an ex vivo peptide-MHC class II tetramer approach. Results CD4+ T cells in allergic subjects are directed to a broad range of TGP epitopes characterized by defined immunodominance hierarchy patterns and with distinct functional profiles that depend on the epitope recognized. Epitopes that are restricted specifically to either TH2 or TH1/TR1 responses were identified. Allergen-specific immunotherapy was associated with preferential deletion of allergen-specific TH2 cells and without a significant change in the frequency of TH1/TR1 cells. Conclusions Preferential allergen-specific TH2 cell deletion after repeated high-dose antigen stimulation can be another independent mechanism to restore tolerance to allergen during immunotherapy.",
keywords = "CD4, Immunotherapy, T cells, allergy, epitope, ex vivo, peptide-MHC class II tetramer, peripheral tolerance, pollen",
author = "Erik Wambre and Delong, {Jonathan H.} and James, {Eddie A.} and Nadia Torres-Chinn and Wolfgang Pf{\"u}tzner and Christian M{\"o}bs and Durham, {Stephen R.} and Till, {Stephen J.} and David Robinson and Kwok, {William W.}",
note = "Funding Information: Disclosure of potential conflict of interest: E. Wambre has been supported by one or more grants from the National Institutes of Health (NIH) and has received a grant for travel from the European Academy of Allergy and Clinical Immunology (EAACI)–World Allergy Organization (WAO) . W. Pf{\"u}tzner is employed by the Department of Dermatology and Allergology, Philipps University, Marburg, Germany, and has received one or more grants from or has one or more grants pending with the German Research Association (DFG). S. R. Durham has received consultancy fees from Stallergenes, GlaxoSmithKline, Boehringer Ingelheim, Circassia, and Merck; has received research support from ALK-Abell{\'o}, Novartis, Stallergenes (Spain), and Letti (Spain) ; and has received lecture fees from Merck. S. J. Till has received one or more grants from or has one or more grants pending with ALK-Abell{\'o}. D. Robinson has been supported by one or more grants from the National Institute of Allergy and Infectious Diseases (NIAID) and is employed by and has received one or more payments for travel/accommodations/meeting expenses from Virginia Mason Medical Center. W. W. Kwok has been supported by one or more grants from, has received support for travel from, and is employed by the Benaroya Research Institute. The rest of the authors declare that they have no relevant conflicts of interest. Funding Information: Supported by National Institutes of Health (NIH) contract HHSN272200700046C and NIH grant AI095074 . ",
year = "2014",
month = mar,
doi = "10.1016/j.jaci.2013.10.054",
language = "English",
volume = "133",
pages = "872--879.e7",
journal = "Journal of Allergy and Clinical Immunology",
issn = "0091-6749",
publisher = "Elsevier Inc.",
number = "3",
}