HELIGMOSOMOIDES POLYGYRUS BAKERI INFECTION ACTIVATES COLONIC FOXP3+ T CELLS ENHANCING THEIR CAPACITY TO PREVENT COLITIS

摘要

Helminthic infections protect mice from colitis in murine models of inflammatory bowel disease and also may protect people. Helminths like H. bakeri (Hpb) can induce Tregs. Experiments explored if Hpb infection could protect mice from colitis through activation of colonic Treg and examined mechanisms of action. We showed that Hpb infection increased the number of T cells expressing Foxp3 in the colon. More importantly, Foxp3+/IL10- and Foxp3+/IL10+ T cell subsets isolated from the colon of Hpb infected mice prevented colitis when adoptively transferred into a murine model of inflammatory bowel disease, while Tregs from uninfected mice could not provide protection. Only the transferred colonic Foxp3+/IL10- T cells from Hpb infected mice readily accumulated in the colon and MLN of recipient mice, and they reconstituted the Foxp3+/IL10- and Foxp3+/IL10+ T cell subsets. However, transferred Foxp3+/IL10+ T cells disappeared. IL10 expression by Foxp3+ T cells was necessary for colitis prevention. Thus, Hpb infection activates colonic Foxp3+ T cells making them highly regulatory. The Foxp3+ T cells that fail to express IL10 may be critical for populating the colon with the Foxp3+/IL10+ T cells, which are required to control colitis.