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 spiralis-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. spiralis-infected [Inf(+)Foxp3(+)] or uninfected [Inf(-)Foxp3(+)] mice into the tail veins of C57BL/6 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 (Klrg1, Capg, GARP, Gzmb, OX40) than did Inf(-)Foxp3(+) cells. CONCLUSION/SIGNIFICANCE: T. spiralis infection promotes the proliferation and functional activation of T(reg) cells. Parasite-induced T(reg) cells migrate to the inflammation site and suppress immune responses more effectively than non-parasite-induced 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.