Asthma and gender impact accumulation of T cell subtypes

Matthew J Loza,Eugene R Bleecker,Susan Foster,Stephen P Peters,Raymond B Penn

doi:10.1186/1465-9921-11-103

Matthew J Loza, Eugene R Bleecker + Show 3 more

Open Access

https://doi.org/10.1186/1465-9921-11-103

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Journal: Respiratory research	Publication Date: Jul 28, 2010
Citations: 27	License type: cc-by

Affiliation: Wake Forest University

Abstract

BackgroundThe "Th2 hypothesis for asthma" asserts that an increased ratio of Th2:Th1 cytokine production plays an important pathogenic role in asthma. Although widely embraced, the hypothesis has been challenged by various empirical observations and has been described as overly simplistic. We sought to establish whether CD3+CD28-mediated and antigen-independent accumulation of type 1 and type 2 T cells differs significantly between nonasthmatic and asthmatic populations.MethodsAn ex vivo system was used to characterize the regulation of IFN-γ-producing (type 1) and IL-13-producing (type 2) T cell accumulation in response to CD3+CD28 and IL-2 stimulation by flow cytometry.ResultsIL-13-producing T cells increased in greater numbers in response to antigen-independent stimulation in peripheral blood lymphocytes from female atopic asthmatic subjects compared with male asthmatics and both male and female atopic non-asthmatic subjects. IFN-γ+ T cells increased in greater numbers in response to either antigen-independent or CD3+CD28-mediated stimulation in peripheral blood lymphocytes from atopic asthmatic subjects compared to non-asthmatic subjects, regardless of gender.ConclusionsWe demonstrate that T cells from asthmatics are programmed for increased accumulation of both type 2 and type 1 T cells. Gender had a profound effect on the regulation of type 2 T cells, thus providing a mechanism for the higher frequency of adult asthma in females.

Highlights

The “Th2 hypothesis for asthma” asserts that an increased ratio of Th2:Th1 cytokine production plays an important pathogenic role in asthma
CD3+CD28-mediated stimulation To test whether T cell subsets in freshly isolated Peripheral blood lymphocytes (PBL) differ in their response to antigenic stimulation, PBL were stimulated with CD3 and CD28 monoclonal antibody to mimic efficient antigenic stimulation by professional antigen-presenting cells
The median proportion of IFN-g+ T cells after 5-day culture was significantly higher in asthmatics than in control subjects

Summary

Introduction

The “Th2 hypothesis for asthma” asserts that an increased ratio of Th2:Th1 cytokine production plays an important pathogenic role in asthma. After allergen challenge, elevated levels of the type 2 cytokines interleukin (IL)-4 and IL-13 are found in the airways of asthma subjects, associated with an influx of type 2 cells and eosinophils [1,2,3]. Several observations suggest that the “Th2 hypothesis” as applied to asthma is overly simplistic. The ratio of type 2 cytokines to interferon (IFN)-g is higher in asthmatics than in nonasthmatic subjects, levels of both cytokines are often dramatically increased in allergen-challenged asthmatics [4,5].

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