Different profiles of IL-10+IFN-gamma-IL-4-CD4+ T cells in the peripheral blood in atopic and non-atopic asthmatics.
ABSTRACT The impaired production of interleukin (IL) 10 from regulatory T cells has been proposed as a causal mechanism of asthma. Although IL-10-producing (IL-10+) T cells are detectable in the peripheral blood, their significance in the pathophysiology of asthma remains uncertain.
This study aimed to investigate the profile of circulating IL-10+CD4+ T cells in atopic and non-atopic asthma.
Atopic and non-atopic asthmatics were divided into a mild and severe group. Their peripheral blood mononuclear cells (PBMCs) were stimulated with anti-CD3 and anti-CD28 antibodies and then processed for triple cytokine flow cytometry directed to IL-10, interferon (IFN) gamma and IL-4.
IL-10+CD4+ cells were exclusively detected in the IFN-gamma-IL-4- population. In atopic asthma, the frequency of IL-10+IFN-gamma-IL-4-CD4+ cells in the severe group was significantly lower than that in the mild group. The frequency of IL-10+IFN-gamma-IL-4-CD4+ cells in the severe group was not significantly different from that in the mild group of those with non-atopic asthma. The frequency of IL-4+IFN-gamma-IL-10-CD4+ cells (Th2) was significantly higher in the group with mild atopic asthma than in that with mild non-atopic asthma. IFN-gamma+IL-4-IL-10-CD4+ cells (Th1) did not differ between groups, irrespective whether the subjects suffered from atopic or non-atopic asthma.
IL-10+CD4+ cells in PBMCs may be distinct from Th1 or Th2 and likely have the profile of regulatory T cells. The differential association of IL-10+IFN-gamma-IL-4-CD4+ cells with clinical severity between atopic and non-atopic asthma implies that its pathophysiological significance may differ among asthma phenotypes.
- Clinical & Experimental Allergy 01/1998; 28(1):10-8. · 4.79 Impact Factor
Article: Tregs and allergic disease.[show abstract] [hide abstract]
ABSTRACT: Allergic diseases such as asthma, rhinitis, and eczema are increasing in prevalence and affect up to 15% of populations in Westernized countries. The description of Tregs as T cells that prevent development of autoimmune disease led to considerable interest in whether these Tregs were also normally involved in prevention of sensitization to allergens and whether it might be possible to manipulate Tregs for the therapy of allergic disease. Current data suggest that Th2 responses to allergens are normally suppressed by both CD4+CD25+ Tregs and IL-10 Tregs. Furthermore, suppression by these subsets is decreased in allergic individuals. In animal models, Tregs could be induced by high- or low-dose inhaled antigen, and prior induction of such Tregs prevented subsequent development of allergen sensitization and airway inflammation in inhaled challenge models. For many years, allergen-injection immunotherapy has been used for the therapy of allergic disease, and this treatment may induce IL-10 Tregs, leading to both suppression of Th2 responses and a switch from IgE to IgG4 antibody production. Improvements in allergen immunotherapy, such as peptide therapy, and greater understanding of the biology of Tregs hold great promise for the treatment and prevention of allergic disease.Journal of Clinical Investigation 12/2004; 114(10):1389-97. · 12.81 Impact Factor
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ABSTRACT: Although IL-10 is known as an immunoregulatory cytokine produced by various cells including T cells, its basic profile in atopic asthma remains uncertain. Objective: The profiles of IL-10 production in circulating CD4+ T cells of atopic asthmatics were investigated with respect to clinical severity. Forty atopic asthmatics were divided into three groups: mild, and severe but stable and severe unstable asthmatics. Eosinophils were counted in the peripheral blood and sputum, and exhaled nitric oxide was assessed. PBMCs were stimulated with or without anti-CD3 and anti-CD28 antibodies and then processed for detecting IL-10-producing CD4+ cells using flow cytometry. There was no difference in the eosinophil count in blood or sputum and in nitric oxide level among the three groups. IL-10-producing CD4+ cells were mainly detected in a CD45RO+ memory population. The frequency of IL-10-producing cells after stimulation was significantly lower in the severe unstable group compared to the mild group. In addition, the frequency of IL-10-producing cells in the severe unstable group was significantly lower than that in the severe stable group despite the fact that both groups received similar treatments with high-dose inhaled corticosteroids. The IL-10 production of CD4+CD45RO+ cells in response to dexamethasone did not differ among the three groups. IL-10-producing CD4+CD45RO+ cells in the peripheral blood are decreased in severe unstable asthmatics, which is not explained by the effect of high-dose inhaled corticosteroid medication.International Archives of Allergy and Immunology 09/2004; 134(4):295-302. · 2.25 Impact Factor