Abstract

BackgroundAllergic sensitisation has been ascribed to a dysregulated relationship between allergen-specific Th1, Th2 and regulatory T cells. We sought to utilise our short-term CD154 detection method to further analyse the relationship between these T cell subsets and investigate differences between seasonal and perennial allergens. Using peripheral blood samples from grass-allergic, cat-allergic and healthy non-atopic subjects, we compared the frequencies and phenotype of CD154-positive T helper cells following stimulation with seasonal (grass) and perennial (cat dander) allergens.ResultsWe identified a higher frequency of CD154+ T cells in grass-allergic individuals compared to healthy controls; this difference was not evident following stimulation with cat allergen. Activated Th1, Th2 and Tr1-like cells, that co-express IFNγ, IL4 and IL10, respectively, were identified in varying proportions in grass-allergic, cat-allergic and non-allergic individuals. We confirmed a close correlation between Th1, Th2 and Tr1-like cell frequency in non-allergic volunteers, such that the three parameters increased together to maintain a low Th2: Th1 ratio. This relationship was dysregulated in grass-allergic individuals with no correlation between the T cell subsets and a higher Th2: Th1 ratio. We confirmed previous reports of a late-differentiated T cell phenotype in response to seasonal allergens compared to early-differentiated T cell responses to perennial allergens.ConclusionsThe findings confirm our existing work illustrating an important balance between Th1, Th2 and Tr1-like responses to allergens in health, where Th2 responses are frequently observed, but balanced by Th1 and regulatory responses. We confirm previous tetramer-based reports of phenotypic differences in T cells responding to seasonal and perennial allergens.

Highlights

  • Allergic sensitisation has been ascribed to a dysregulated relationship between allergen-specific Th1, Th2 and regulatory T cells

  • We showed that T cell responses to birch allergen in health are of mixed phenotype, but tightly maintained at a low Th2: Th1 ratio

  • Th2 responses to grass, but not cat allergen, have a latedifferentiated phenotype We investigated the phenotype of responding CD154+ and CD154+cytokine+ T cell populations following allergen stimulation using the expression of cell surface marker CD27

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Summary

Introduction

Allergic sensitisation has been ascribed to a dysregulated relationship between allergen-specific Th1, Th2 and regulatory T cells. Results: We identified a higher frequency of CD154+ T cells in grass-allergic individuals compared to healthy controls; this difference was not evident following stimulation with cat allergen. We confirmed a close correlation between Th1, Th2 and Tr1-like cell frequency in non-allergic volunteers, such that the three parameters increased together to maintain a low Th2: Th1 ratio This relationship was dysregulated in grass-allergic individuals with no correlation between the T cell subsets and a higher Th2: Th1 ratio. We recently presented the first detailed description of CD154+ T cells after short-term birch allergen stimulation in nonallergic controls and birch pollinosis patients [3] Using this method, we showed that T cell responses to birch allergen in health are of mixed phenotype, but tightly maintained at a low Th2: Th1 ratio. The relationship was dysregulated in birch pollinosis, with a higher Th2: Th1 ratio and abrogation of the IL-10 response

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