Protection of IFN-gamma signaling-deficient NOD mice from diabetes by cyclophosphamide.
Non-obese diabetic (NOD) mice that are genetically deficient in either IFN-gamma or beta chain of the IFN-gammaR develop diabetes with similar kinetics to wild-type NOD mice. In the current study, we demonstrated that treatment of IFN-gamma signaling-deficient NOD mice with cyclophosphamide (CY) not only fails to induce acute diabetes but also confers permanent protection from diabetes. Protection was mediated by the preferential generation of regulatory T cells (Treg cells) that are capable of suppressing the diabetogenic process, with no change in the total number and function of Treg cells. Moreover, CY treatment of IFN-gamma signaling-deficient NOD mice reversed the ongoing pathogenic process and eliminated cellular infiltrates of pancreatic islets. While these results have been derived using a genetically modified mouse model of diabetes, they indicate that knowledge of host genetic factors and environmental factors influencing the development of Type I diabetes mellitus may provide a rational approach to develop a means to reverse the development of Type I diabetes in human.
Mori
Yoshiko
Y
Laboratory for Autoimmune Regulation, RIKEN Center for Allergy and Immunology, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
Kato
Takako
T
Kodaka
Tetsuro
T
Kanagawa
Edith M
EM
Hori
Shohei
S
Kanagawa
Osami
O
D000818:Animals; D003520:Cyclophosphamide / Q000008:administration & dosage*; D003921:Diabetes Mellitus, Experimental / Q000209:etiology / Q000235:genetics / Q000517:prevention & control*; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology / Q000235:genetics / Q000517:prevention & control*; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007371:Interferon-gamma / Q000172:deficiency* / Q000235:genetics; D007515:Islets of Langerhans / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D050378:T-Lymphocytes, Regulatory
D007166:Immunosuppressive Agents; D007371:Interferon-gamma; D003520:Cyclophosphamide