Title | Allergen-specific CD8+ T cells and atopic disease |
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Type | Journal article |
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Authors | Seneviratne, Suranjith L, Jones, Louise, King, Abigail S, Black, Antony, Powell, Sheila, McMichael, Andrew J, Ogg, Graham S and Black, Antony |
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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-γ 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. |
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Journal | The Journal of clinical investigation |
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Journal citation | 110 (9), pp. 1283-1291 |
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ISSN | 021-9738 |
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| 1558-8238 |
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Year | 2002 |
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Publisher | American Society for Clinical Investigation |
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Publisher's version | License CC BY 4.0 File Access Level Open (open metadata and files) |
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Digital Object Identifier (DOI) | https://doi.org/10.1172/JCI15753 |
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Publication dates |
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Published | 2002 |
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