CD4+CD25+ regulatory T cells reverse established allergic airway inflammation and prevent airway remodeling

Background: CD4(+)CD25(+) regulatory T cells can inhibit excessive T-cell responses in vivo. We have previously demonstrated that prophylactic administration of CD4+CD25+ regulatory T cells suppresses the development of acute allergen-induced airway inflammation in vivo. Objective: We sought to determine the effect of therapeutic transfer of CD4(+)CD25(+) regulatory T cells on established pulmonary inflammation and the subsequent development of airway remodeling. Methods: CD4(+)CD25(+) cells were transferred after the onset of allergic inflammation, and airway challenges were continued to induce chronic inflammation and airway remodeling. Results: Administration of CD4(+)CD25(+) regulatory T cells reduced established lung eosinophilia, T(H)2 infiltration, and expression of IL-5, IL-13, and TGF-beta. Moreover, subsequent mucus hypersecretion and peribronchial collagen deposition were reduced after prolonged challenge. In contrast, transfer of CD4(+)CD25(+) regulatory T cells had no effect on established airway hyperreactivity either 7 days or 4 weeks after transfer. Conclusions: In this study we demonstrate for the first time that therapeutic transfer of CD4(+)CD25(+) regulatory T cells can resolve features of chronic allergen-induced inflammation and prevent development of airway remodeling.