Fluticasone propionate increases suppression of allergen-driven T cell proliferation by CD4+CD25+ T cells

Abstract

Listen

Translate article

Rationale Corticosteroids are the main anti-inflammatory treatment for asthma and allergic diseases, and have been reported to increase the suppressive cytokine IL-10. We have previously reported less suppression by CD4+CD25+ regulatory T cells from atopics compared to non-atopics. We asked whether the steroid fluticasone propionate (FP) could increase activity of naturally occurring CD4+CD25+ regulatory T cells. Methods CD4+CD25+ and CD4+CD25- T cells were isolated by immunomagnetic columns from atopic and non-atopic donors. The effects of different concentrations of FP on CD4+CD25- T cells, co-cultures of CD25+ and CD25- T cells, and the effect of pre-incubation of CD4+CD25+ T cells with FP on subsequent suppression of allergen-stimulated CD4+CD25- T cells were examined. Results FP suppressed allergen stimulated proliferation CD4+CD25- in a dose dependent fashion with an IC50 of 10 -9M. Addition of low dose FP to mixed cultures did not affect suppression of allergen induced proliferation by CD4+CD25+, which was significantly less in atopic than in non-atopic donors. However, pre-incubation of CD4+CD25+ T cells in 10 -7M FP for 24 hours significantly increased their suppressive ability in allergen cultures, (p<0.01 for atopics and 0.05 for non-atopics). This increase in suppression was associated with an increase in allergen-stimulated IL-10 production by CD4+CD25+ that were pre-incubated in FP. Conclusions Fluticasone propionate increases the suppressive activity of CD4+CD25+ regulatory T cells for allergen-stimulation of CD4+CD25- T cells, and this may be by increasing their production of IL-10.