Decreased percentage of CD4+Foxp3+TGF-β+ and increased percentage of CD4+IL-17+ cells in bronchoalveolar lavage of asthmatics

Asthma 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.The 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.Twenty 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.The 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).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(+)TGF-β(+).