Mechanisms of asthma and allergic inflammationFluticasone propionate increases CD4+CD25+ T regulatory cell suppression of allergen-stimulated CD4+CD25− T cells by an IL-10–dependent mechanism☆
Section snippets
Methods
Volunteers were recruited from among the staff of Imperial College London and by advertisement. The study was approved by the Ethics Committee of the Royal Brompton and Harefield Hospitals NHS Trust. Volunteers were assessed by questionnaire on allergic symptoms and skin prick tests (ALK, Horsholm, Denmark) and assigned to atopic (positive history and at least one positive skin prick test result of 3 mm or larger in diameter than that elicited by the negative control) or nonatopic (no history
Effect of FP on allergen-stimulated proliferation of CD4+CD25− T cells
Inhibitory effects of corticosteroids on T-cell proliferation are well described.11 However, there are no reports of inhibition of isolated CD4+CD25− T cells. We previously showed that these CD4+CD25− T cells, in the absence of regulatory CD4+CD25+ T cells, show increased proliferation to allergen stimulation when compared with unseparated PBMCs.17 First, we examined the effects of different concentrations of FP on allergen-stimulated proliferation of CD4+CD25− T cells from 6 atopic subjects.
Discussion
We have recently reported that the suppressive activity of CD4+CD25+ regulatory T cells in allergen-stimulated in vitro cultures is diminished when cells from atopic allergic donors are compared with those from nonatopic control subjects.17 Corticosteroids are the mainstay of anti-inflammatory treatment for asthma. We now report that the corticosteroid FP inhibited allergen-stimulated proliferation of CD4+CD25− T cells. Furthermore, preincubation with FP increased the suppressive activity of CD4
Acknowledgements
We thank Drs Malcolm Johnson, Ian Adcock, Anne O'Garra, Catherine Hawrylowicz, Clare Lloyd, Eleanor Ling, David Ahern, Carol Pridgeon, Margaret Dallman, Clare Notley, Mark Larche, and Barry Kay for discussions of the study and Justine Arbery, RGN, for help with volunteer recruitment.
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Supported by a grant from GlaxoSmithKline. DN and DSR are supported by the Wellcome Trust, United Kingdom.
Disclosure of potential conflict of interest: X. D. Nguyen and D. S. Robinson received support from GlaxoSmithKline for attendance at scientific meetings. D. S. Robinson has received support from GlaxoSmithKline for research on regulatory T cells and honoraria for educational speaking engagements and is on the Speakers' Bureau for GlaxoSmithKline, AstraZeneca, 3M, and Schering Plough.