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-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

High IFN-γ production by CD8+ T cells and early sensitization among infants at high risk of atopy

“…36 A recent study using class I MHC tetramer technology has also implicated CD8 + T cells responsive to Der p 1 allergen as determinants of the severity of allergic disease in HDM-sensitized adults. 37 In a previous study, we demonstrated that although expression of the IFN-c gene is developmentally constrained in neonatal CD4 + T cells via hypermethylation of CpG dinucleotide sites in the proximal promoter, this control mechanism does not appear to operate to the same degree in neonatal CD8 + T cells, which are capable of production of IFN-c at levels close to the adult normal range. 17 We have confirmed this observation, demonstrating that in the order of 90% of the polyclonal IFN-c response of CBMC is attributable to CD8 + cells, which suggests that the association defined here between atopy development in children with HR and elevated IFN-c production is related principally to variations in CD8 + as opposed to CD4 + T-cell function.…”

T-cell responses to allergens

“…These fluorochrome-conjugated complexes bind to T cells with defined TCR specificities and are emerging as a useful tool for identifying and enumerating circulating allergen-specific CD4 1 T cells by flow cytometry ( Fig 5). 121,122 However, to date only a limited panel of MHC class II molecules is available as tetramers, and because these reagents can only be used in subjects expressing specific HLA class II alleles, it is necessary to screen many patients to identify sufficient subjects for a study.…”

SLIT Prevents the Development of Eczema in Percutaneous Allergen-Sensitized Mice

“…In this DF-induced AD model, we have previously shown that CD8 þ T cells producing IFN-g are essential for the development of AD skin inflammation (Hennino et al, 2007). The importance of CD8 þ T cells has been previously described in the physiopathology of the human disease (Akdis et al, 1999;Seneviratne et al, 2002;Hennino et al, 2011). Upon DF skin sensitization, CD8 þ T cells are induced in draining lymph nodes and recruited in the challenged skin where they initiate the AD-like skin inflammatory reaction.…”