Overexpression of fibrinogen-like protein 2 protects against T cell-induced colitis.

AIM

To determine the effect of overexpression of fibrinogen-like protein 2 (FGL2) on regulatory T cell (Treg) and effector T (Teff) cell function on T cell-induced colitis in mice.

METHODS

Treg and Teff cells from , , and mice were purified by FACS. They were studied for immunosuppressive activity and cell proliferation and for their effects on the development and prevention of T cell-induced colitis in mice.

RESULTS

, Treg had enhanced immunosuppressive activity, and Teff had reduced proliferation to alloantigen stimulation. Transfer of Teff from C57Bl/6J mice () into mice produced both clinical and histologic colitis with dense infiltrates of CD3 T cells, crypt abscesses and loss of goblet cells. Treg prevented the development of T cell-induced colitis, whereas and Treg were only partially protective. In mice that received Treg, the ratio of Foxp3 to CD3 cells was increased both in the colon and in mesenteric lymph nodes, and Teff cell proliferation as determined by staining with Ki67 was reduced. Teff cells from mice did not produce colitis.

CONCLUSION

Here we show that Teff are hypoproliferative and do not induce colitis. We further demonstrate that Treg prevent colitis in contrast to Treg, which were only partially protective. These studies collectively provide a rationale for exploring the use of FGL2 or Treg expressing high levels of FGL2 in the treatment of inflammatory bowel disease.