title: Allergen-specific CD8(+) T cells and atopic disease.
abstract: Considerable evidence suggests that IL-10 may have a role in the manifestation of atopic disease. We sought to test the hypothesis that at the single cell level, allergen-specific T cells have diminished IL-10 production capacity in severely affected atopics compared with asymptomatic atopics. We defined three A*0201-restricted Der p 1 CD8(+) T cell epitopes. Using human leukocyte antigen-A*0201-peptide (HLA-A*0201-peptide) tetrameric complexes and enzyme-linked immunospot assays to analyze peripheral blood mononuclear cells from A*0201-positive severely symptomatic atopics, asymptomatic atopics, and nonatopic controls, we observed a significant association between the frequency of the Der p 1-specific CD8(+) T cells and disease activity. The specific T cells expressed an antigen-experienced cell surface phenotype, and 45.7% were positive for cutaneous lymphocyte-associated antigen. The specific T cells were able to produce IFN-gamma efficiently, but their IL-10 production was significantly reduced in severely affected atopics. In contrast, viral-specific CD8(+) T cells were able to produce equivalent amounts of IL-10 in the severely affected atopics compared with asymptomatic atopics and nonatopics. Through defining the first human atopic allergen HLA class I epitopes, we have provided a possible cellular mechanism to link the previous association of low IL-10 levels and severe atopic disease. These data are consistent with a role for CD8(+) T cells in atopic disease pathogenesis and may provide a basis for future T cell immunotherapy strategies.
authors.affiliation: Weatherall Institute of Molecular Medicine, Oxford, United Kingdom.
authors.forename: Suranjith L
authors.initials: SL
authors.lastname: Seneviratne
authors.forename: Louise
authors.initials: L
authors.lastname: Jones
authors.forename: Abigail S
authors.initials: AS
authors.lastname: King
authors.forename: Antony
authors.initials: A
authors.lastname: Black
authors.forename: Sheila
authors.initials: S
authors.lastname: Powell
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: McMichael
authors.forename: Graham S
authors.initials: GS
authors.lastname: Ogg
mesh_terms: D000328:Adult; D000485:Allergens / Q000276:immunology*; D039741:Antigens, Dermatophagoides / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; D060829:Arthropod Proteins; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003546:Cysteine Endopeptidases; D016207:Cytokines / Q000096:biosynthesis; D018984:Epitopes, T-Lymphocyte; D005260:Female; D015234:HLA-A Antigens / Q000276:immunology; D006801:Humans; D006967:Hypersensitivity / Q000209:etiology*; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology
chemical_list: D000485:Allergens; D039741:Antigens, Dermatophagoides; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; D060829:Arthropod Proteins; C063419:CTAGE1 protein, human; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; D008562:Membrane Glycoproteins; D003546:Cysteine Endopeptidases; C451162:Dermatophagoides pteronyssinus antigen p 1