Fluticasone propionate increases CD4CD25 T regulatory cell suppression of allergen-stimulated CD4CD25 T cells by an IL-10-dependent mechanism

Corticosteroids are the most effective anti-inflammatory therapy for allergic diseases, and these drugs inhibit TH2 T-cell activation. We previously reported that CD4+CD25+ T cells from atopic donors suppressed allergen-stimulated T cells less than those from nonatopic donors. We sought to determine...

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Bibliographic Details
Published in:Journal of allergy and clinical immunology 2004-08, Vol.114 (2), p.296-301
Main Authors: Dao Nguyen, X, Robinson, Douglas S
Format: Article
Language:English
Subjects:
Albuterol - analogs & derivatives
Albuterol - pharmacology
Allergens - immunology
Androstadienes - pharmacology
CD4 Antigens - analysis
Fluticasone
Humans
Interleukin-10 - physiology
Lymphocyte Activation - drug effects
Receptors, Interleukin-2 - analysis
Salmeterol Xinafoate
T-Lymphocytes - immunology
T-Lymphocytes, Regulatory - drug effects
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Summary:Corticosteroids are the most effective anti-inflammatory therapy for allergic diseases, and these drugs inhibit TH2 T-cell activation. We previously reported that CD4+CD25+ T cells from atopic donors suppressed allergen-stimulated T cells less than those from nonatopic donors. We sought to determine the effect of fluticasone propionate (FP) on allergen-stimulated CD4+CD25- T cells and on the suppressive ability of CD4+CD25+ T cells. CD4+CD25+ and CD4+CD25- T cells were separated from peripheral blood of atopic and nonatopic volunteers and cultured alone or mixed in the presence of allergen. Effects of FP were assessed by means of addition to cultures or preincubation with CD4+CD25+ T cells. FP inhibited allergen-stimulated proliferation of CD4+CD25- T cells in a dose-dependent manner. Preincubation of CD4+CD25+ T cells in FP increased subsequent suppressive activity of these cells in allergen-stimulated cultures with CD4+CD25- T cells. This effect was seen when cells were obtained from both nonatopic and atopic donors but was less for cells obtained from atopic individuals. Prior exposure of CD4+CD25+ T cells to FP also increased subsequent IL-10 production by these cells when stimulated with allergen, and addition of anti-IL-10 antibody reversed the steroid-induced enhancement of suppression in mixed cultures. Increased suppression by CD4+CD25+ T cells might play a role in anti-inflammatory effects of corticosteroids in asthma and allergic diseases.
ISSN:0091-6749
DOI:10.1016/j.jaci.2004.04.048