Abstract
Helminthic infections protect mice from colitis in murine models of inflammatory bowel disease and also may protect people. Helminths like Heligmosomoides polygyrus bakeri can induce regulatory T cells (Treg). Experiments explored whether H. polygyrus bakeri infection could protect mice from colitis through activation of colonic Treg and examined mechanisms of action. We showed that H. polygyrus bakeri infection increased the number of T cells expressing Foxp3 in the colon. More importantly, Foxp3(+)/IL-10(-) and Foxp3(+)/IL-10(+) T cell subsets isolated from the colon of H. polygyrus bakeri-infected mice prevented colitis when adoptively transferred into a murine model of inflammatory bowel disease, whereas Treg from uninfected mice could not provide protection. Only the transferred colonic Foxp3(+)/IL-10(-) T cells from H. polygyrus bakeri-infected mice readily accumulated in the colon and mesenteric lymph nodes of recipient mice, and they reconstituted the Foxp3(+)/IL-10(-) and Foxp3(+)/IL-10(+) T cell subsets. However, transferred Foxp3(+)/IL-10(+) T cells disappeared. IL-10 expression by Foxp3(+) T cells was necessary for colitis prevention. Thus, H. polygyrus bakeri infection activates colonic Foxp3(+) T cells, making them highly regulatory. The Foxp3(+) T cells that fail to express IL-10 may be critical for populating the colon with the Foxp3(+)/IL-10(+) T cells, which are required to control colitis.