Frequency of Foxp3⁺CD4⁺CD25⁺ T cells is associated with the phenotypes of allergic asthma

Abstract

BACKGROUND AND OBJECTIVE: A forkhead/winged-helix family transcriptional repressor, Foxp3, is highly expressed on CD4(+)CD25(+) T regulatory cells. The role of Foxp3(+)CD4(+)CD25(+) T regulatory cells in asthma remains to be elucidated. Using mouse models and peripheral blood mononuclear cells (PBMC) from subjects with allergic asthma, we aimed to explore whether Foxp3(+)CD4(+)CD25(+) T regulatory cells associate with asthma phenotypes. METHODS: Foxp3(+)CD4(+)CD25(+) T cells were detected by FACS and the correlation between the frequency of Foxp3(+)CD4(+)CD25(+) T cells and asthma phenotypes was assessed. RESULTS: The frequency of Foxp3(+)CD4(+)CD25(+) T cells among total CD4(+)CD25(+) T cells in the lungs showed an inverse correlation with eosinophilic inflammation in BALB/c, A/J and C57BL/6 strains. In addition, the frequency of Foxp3(+)CD4(+)CD25(+) T cells was inversely correlated with BHR and allergen-specific IgE levels in the serum of A/J mice. In BALB/c mice, the frequency of Foxp3(+)CD4(+)CD25(+) T cells correlated with the level of IL-10 in BAL fluid. The inverse correlation between the frequency of Foxp3(+)CD4(+)CD25(+) T cells and eosinophilic inflammation disappeared when mice were treated with anti-IL-10 receptor mAb during allergen challenge. Interestingly, intracellular cytokine staining of lung cells revealed that IL-10 was predominantly produced by Foxp3(-)CD4(+)CD25(+) T cells. The frequency of Foxp3(+)CD4(+)CD25(+) T cells among total CD4(+)CD25(+) T cells in PBMC of asthmatics was significantly lower than that of healthy subjects, although there was no significant correlation between the frequency of Foxp3(+)CD4(+)CD25(+) T cells and asthma severity. CONCLUSIONS: These results suggest a role for lung Foxp3(+)CD4(+)CD25(+) T cells in the regulation of asthma phenotypes, presumably through an IL-10-mediated mechanism.