Parasitic Nematode-Induced CD4+Foxp3+T Cells Can Ameliorate Allergic Airway Inflammation

Background: The recruitment of CD4(+)CD25(+)Foxp3(+)T (T-reg) cells is one of the most important mechanisms by which parasites down-regulate the immune system. Methodology/Principal Findings: We compared the effects of T-reg cells from Trichinella spira/is-infected mice and uninfected mice on experimental allergic airway inflammation in order to understand the functions of parasite-induced T-reg cells. After four weeks of T. spiralis infection, we isolated Foxp3-GFP-expressing cells from transgenic mice using a cell sorter. We injected CD4(+)Foxp3(+) cells from T. spira/is-infected [Inf(+)Foxp3(+)] or uninfected [Inf(-)Foxp3 (+)] mice into the tail veins of C578U6 mice before the induction of inflammation or during inflammation. Inflammation was induced by ovalbumin (OVA)-alum sensitization and OVA challenge. The concentrations of the Th2-related cytokines IL-4, IL-5, and IL-13 in the bronchial alveolar lavage fluid and the levels of OVA-specific IgE and IgG1 in the serum were lower in mice that received intravenous application of Inf(+)Foxp3(+) cells [IV(inf):+(+) group] than in control mice. Some features of allergic airway inflammation were ameliorated by the intravenous application of Inf(+)Foxp3(+) cells [IV(inf):+(-) group], but the effects were less distinct than those observed in the IV(inf):+(+) group. We found that Inf(+)Foxp3(+) cells migrated to inflammation sites in the lung and expressed higher levels of T-reg-cell homing receptors (CCR5 and CCR9) and activation markers (KIrg1, Capg, GARP, Gzmb, OX40) than did Inf(-)Foxp3(+) cells. Conclusion/Significance: T. spiralis infection promotes the proliferation and functional activation of T-reg cells. Parasiteinduced T-reg cells migrate to the inflammation site and suppress immune responses more effectively than non-parasiteinduced T-reg cells. The adoptive transfer of Inf(+)Foxp3 cells is an effective method for the treatment and prevention of allergic airway diseases in mice and is a promising therapeutic approach for the treatment of allergic airway diseases.