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


OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
Increased suppression by CD4+CD25+ T cells might play a role in anti-inflammatory effects of corticosteroids in asthma and allergic diseases.
Dao Nguyen
X
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Leukocyte Biology Section, Division of Biomedical Sciences and Allergy and Clinical Immunology, National Heart and Lung Institute, Faculty of Medicine, Imperial College, London, United Kingdom.
Robinson
Douglas S
DS
D000420:Albuterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D000485:Allergens / Q000276:immunology*; D000730:Androstadienes / Q000494:pharmacology*; D015704:CD4 Antigens / Q000032:analysis*; D000068298:Fluticasone; D006801:Humans; D016753:Interleukin-10 / Q000502:physiology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D015375:Receptors, Interleukin-2 / Q000032:analysis*; D000068299:Salmeterol Xinafoate; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects*
D000485:Allergens; D000730:Androstadienes; D015704:CD4 Antigens; D015375:Receptors, Interleukin-2; D016753:Interleukin-10; D000068299:Salmeterol Xinafoate; D000068298:Fluticasone; D000420:Albuterol