AIM To determine the effect of overexpression of fibrinogenlike protein 2(FGL2) on regulatory T cell(Treg) and effector T(Teff) cell function on T cell-induced colitis in Rag1-/-mice.METHODS Treg and Teff cells from f...AIM To determine the effect of overexpression of fibrinogenlike protein 2(FGL2) on regulatory T cell(Treg) and effector T(Teff) cell function on T cell-induced colitis in Rag1-/-mice.METHODS Treg and Teff cells from fgl2-/-, fgl2+/+, and fgl2 Tg mice were purified by FACS. They were studied in vitro for immunosuppressive activity and cell proliferation and in vivo for their effects on the development and prevention of T cell-induced colitis in Rag1-/-mice. RESULTS In vitro, fgl2 Tg Treg had enhanced immunosuppressive activity, and fgl2 Tg Teff had reduced proliferation to alloantigen stimulation. Transfer of Teff from C57Bl/6J mice(fgl2+/+) into Rag1-/-mice produced both clinical and histologic colitis with dense infiltrates of CD3+ T cells, crypt abscesses and loss of goblet cells. Fgl2 Tg Treg prevented the development of T cell-induced colitis, whereas fgl2+/+ and fgl2-/-Treg were only partially protective. In mice that received fgl2 Tg 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 fgl2 Tg mice did not produce colitis. CONCLUSION Here we show that fgl2 Tg Teff are hypoproliferative and do not induce colitis. We further demonstrate that fgl2 Tg Treg prevent colitis in contrast to fgl2+/+ 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.展开更多
基金Supported by the Heart and Stroke Foundation of Canada,No.G-13-0002851the Canadian Institutes of Health Research Training Program in Regenerative Medicine to Bartczak A and Chruscinski Athe Ontario Graduate Scholarship in Science and Technology to Bartczak A
文摘AIM To determine the effect of overexpression of fibrinogenlike protein 2(FGL2) on regulatory T cell(Treg) and effector T(Teff) cell function on T cell-induced colitis in Rag1-/-mice.METHODS Treg and Teff cells from fgl2-/-, fgl2+/+, and fgl2 Tg mice were purified by FACS. They were studied in vitro for immunosuppressive activity and cell proliferation and in vivo for their effects on the development and prevention of T cell-induced colitis in Rag1-/-mice. RESULTS In vitro, fgl2 Tg Treg had enhanced immunosuppressive activity, and fgl2 Tg Teff had reduced proliferation to alloantigen stimulation. Transfer of Teff from C57Bl/6J mice(fgl2+/+) into Rag1-/-mice produced both clinical and histologic colitis with dense infiltrates of CD3+ T cells, crypt abscesses and loss of goblet cells. Fgl2 Tg Treg prevented the development of T cell-induced colitis, whereas fgl2+/+ and fgl2-/-Treg were only partially protective. In mice that received fgl2 Tg 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 fgl2 Tg mice did not produce colitis. CONCLUSION Here we show that fgl2 Tg Teff are hypoproliferative and do not induce colitis. We further demonstrate that fgl2 Tg Treg prevent colitis in contrast to fgl2+/+ 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.
