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|Title:||Identifying the frequency and phenotype of IL-8+ T cells in cat allergic and non-cat allergic subjects|
|Abstract:||Advances in immunotherapy have led to the development of peptide immunotherapy (PIT) which has shown clinical efficacy in a reducing allergic symptoms and providing long-lasting benefits. In mechanistic studies, we identified that PIT reduced the transcription of IL-8 in allergen-specific T cells coinciding with no increase in blood neutrophil counts after a nasal allergen challenge. IL-8 is a chemoattractant that elicits the migration and activation of neutrophils and basophils, causing the release of histamines and leukotrienes which are effector molecules implicated in allergic diseases. We hypothesized that in allergic individuals, a novel T cell subset, ‘Th8’, may exist and are primed to produce and release IL-8 upon allergen exposure. In this study, we determined the frequency and phenotype of allergen-specific IL-8+ T cells through flow cytometry and ELISpot assays in a clinical study with 12 cat allergic and 13 non-cat allergic subjects. In cat allergics, the frequency of IL-8+CD4+ T cells was 2.14±1.02% while non-cat allergics had a frequency of 1.99±0.97% at baseline. Stimulation with cat allergens resulted in a small increase in the frequency of IL-8+ T cells in both groups. In the population of IL-8+ T cells, only a minor subpopulation were allergen-specific as <2% expressed CD154. Allergen-specificity of these cells were also assessed through MHC Class II tetramer staining, which yielded a similar result as 99.7±153.8 TET+IL-8+ T cells/million CD4 were detected in cat allergics compared to 50.9±43.5/million CD4 in non-cat allergics. Phenotyping of IL-8+ T cells suggests that these cells may have similar homing characteristics as Th2 cells due to the expression of CCR4. The presence of IL-8+ T cells detected in the study suggests that there may be a small population of allergen-specific T cells that produce IL-8 upon allergen exposure that contributes to the chemotaxis/activation of neutrophils and basophils, leading to allergic symptoms.|
|Appears in Collections:||Open Access Dissertations and Theses|
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