期刊
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
卷 129, 期 2, 页码 544-U411出版社
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2011.08.034
关键词
Immunotherapy; allergy; pollen; T cells; CD4; peptide-MHC class II tetramer; peripheral tolerance; differentiation stage; ex vivo
资金
- National Institutes of Health [HHSN272200700046C]
Background: The main obstacle to elucidating the role of CD4(+) T cells in allergen-specific immunotherapy (SIT) has been the absence of an adequately sensitive approach to directly characterize rare allergen-specific T cells without introducing substantial phenotypic modifications by means of in vitro amplification. Objective: We sought to monitor, in physiological conditions, the allergen-specific CD4(+) T cells generated during natural pollen exposure and during allergy vaccination. Methods: Alder pollen allergy was used as a model for studying seasonal allergies. Allergen-specific CD4(+) T cells were tracked and characterized in 12 subjects with alder pollen allergy, 6 nonallergic subjects, and 9 allergy vaccine-treated subjects by using peptide-MHC class II tetramers. Results: Allergen-specific CD4(+) T cells were detected in all of the subjects with alder pollen allergy and nonallergic subjects tested. Pathogenic responses-chemoattractant receptor homologous molecule expressed on TH- lymphocytes (CRTH2) expression and T(H)2 cytokine production- are specifically associated with terminally differentiated (CD27(-)) allergen-specific CD4(+) T cells, which dominate in allergic subjects but are absent in nonallergic subjects. In contrast, CD27(+) allergen-specific CD4(+) T cells are present at low frequencies in both allergic and nonallergic subjects and reflect classical features of the protective immune response with high expression of IL-10 and IFN-gamma. Restoration of a protective response during SIT appears to be due to the preferential deletion of pathogenic (CD27(-)) allergen-specific CD4(+) T cells accompanied by IL-10 induction in surviving CD27(+) allergen-specific CD4(+) T cells. Conclusions: Differentiation stage divides allergen-specific CD4(+) T cells into 2 distinct subpopulations with unique functional properties and different fates during SIT. (J Allergy Clin Immunol 2012;129:544-51.)
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