Adaptive Foxp3+ Regulatory T Cell-Dependent and -Independent Control of Allergic Inflammation

SummaryAdaptive Foxp3+ regulatory T (Treg) cells develop during induction of mucosal tolerance and after immunization. Large numbers of Foxp3+ T cells have been found in inflamed tissues. We investigated the role of adaptive Foxp3+ Treg cells in mucosal tolerance and in chronic allergic lung inflammation. We used two strains of mice that are devoid of naturally occurring Treg cells; one is capable of generating adaptive Foxp3+ Treg cells upon exposure to antigen, whereas the other is deficient in both naturally occurring and adaptive Foxp3+ Treg cells. We found that adaptive Foxp3+ Treg cells were essential for establishing mucosal tolerance and for suppressing IL-4 production and lymphoid neogenesis in chronic inflammation, whereas IL-5 production and eosinophilia could be controlled by Foxp3-independent, IFN-γ-dependent mechanisms. Thus, whereas adaptive Foxp3+ Treg cells regulate sensitization to allergens and the severity of chronic inflammation, IFN-γ-producing cells can play a beneficial role in inflammatory conditions involving eosinophils.