Abstract
BackgroundAsthma is a chronic inflammatory disorder of the airways with the proven role of Th2 cells in its pathogenesis. The role and characteristic of different subsets of CD4+ cells is much less known.AimThe aim of the study was to analyze the incidence of different subsets of CD4+ T cells, in particular different subsets of CD4+ cells with the co-expression of different cytokines.MethodsTwenty five stable asthmatic and twelve age-matched control subjects were recruited to the study. Bronchoscopy and bronchoalveolar lavage (BAL) were performed in all study subjects. CD4+ T cells were isolated from BAL fluid by positive magnetic selection. After stimulation simultaneous expression of TGF-β, FoxP3, CD25, IFN-γ, IL-4, TNF-α (set 1); IL-10, FoxP3, CD25, IFN-γ, IL-4, MIP-1β (set 2); IL-17A, IL-8, IFN-γ, IL-4, MIP-1β (set 3) were measured by flow cytometry.ResultsThe percentage of CD4+ cells co-expressing Foxp3 and TGF-β (CD4+Foxp3+TGF-β+ cells) was significantly lower (P = 0.03), whereas the percentage of CD4+IL-17+ cells (P = 0.008), CD4+IL-17+ IFN-γ+ cells (P = 0.047) and CD4+IL-4+ cells (P = 0.01) were significantly increased in asthmatics compared with that seen in healthy subjects. A significantly higher percentage of CD4+Foxp3+ cells from asthma patients expressed IFN-γ (P = 0.01), IL-4 (P = 0.004) and CD25 (P = 0.04), whereas the percentage of CD4+IL-10+ cells expressing Foxp3 was significantly decreased in asthmatics (P = 0.03). FEV1% predicted correlated negatively with the percentage of CD4+IL-17+ cells (r = -0.33; P = 0.046) and positively with CD4+Foxp3+TGF-β+ cells (r = 0.43; P = 0.01).ConclusionsOur results suggest that in the airways of chronic asthma patients there is an imbalance between increased numbers of CD4+IL-17+ cells and Th2 cells and decreased number of CD4+Foxp3+TGF-β+.
Highlights
Asthma is a chronic inflammatory disorder of the airways with the proven role of Th2 cells in its pathogenesis
Our results suggest that in the airways of chronic asthma patients there is an imbalance between increased numbers of CD4+IL-17+ cells and Th2 cells and decreased number of CD4+Foxp3+Tranforming growth factor-β (TGF-β)+
The aim of our study was to analyze the incidence of different subsets of CD4+ T cells in bronchoalveolar lavage (BAL) fluid of asthmatics and healthy subjects, in particular CD4+CD25+Foxp3+ cells, CD4+Foxp3+ cells, CD4+IL-10+IL-4- cells, CD4+TGF-β+ cells, CD4+TGF-β+Foxp3+ cells and CD4+IL-17+ cells together with the co-expression of various cytokines: IFN-γ - a marker of Th1 cells, IL-4 – a marker of Th2 cells, IL-8 (CXCL8) – a chemokine for neutrophils, Macrophage inflammatory protein-1β (MIP-1β) (CCL4) – a chemokine for monocytes and macrophages and tumor necrosis factor-α (TNF-α) - a proinflammatory cytokine
Summary
Asthma is a chronic inflammatory disorder of the airways with the proven role of Th2 cells in its pathogenesis. NTreg got their name because they are always present in the body and constantly perform their function during normal surveillance of selfantigens [4]. They arise in thymus and leave it fully active, ready to inhibit immunological responses. They constitute the population of long-living cells, resident in peripheral organs and one of their main activities is protection against autoimmunological disorders [4]. It should be noted that we still lack precise and specific markers of nTreg cells [6]
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