Cooperation of invariant NKT cells and CD4＋CD25＋ T regulatory cells in prevention of autoimmune diabetes in non-obese diabetic mice treated with α- galactosylceramide  

作　　者：Weipeng Li Fang Ji Yong Zhang Ying Wang Neng Yang Hailiang Ge Fuqing Wang 

机构地区：[1]Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China [2]First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China

出　　处：《Acta Biochimica et Biophysica Sinica》2008年第5期381-390,共10页生物化学与生物物理学报（英文版）

摘　　要：CDld-restricted natural killer T （NKT） cells and CD4＋CD25＋ regulatory T （Treg） cells are two thymus-derived subsets of regulatory T cells that play an important role in the maintenance of self-tolerance. Yet the functional changes of the two subsets of regulatory T cells in the development of diabetes in non-obese diabetic （NOD） mice remain unclear, and how NKT cells and CD4＋CD25＋ Treg cells cooperate functionally in the regulation of autoimmune diabetes is also uncertain. We provide evidence that in NOD mice, an animal model of human type 1 diabetes, the functions of both NKT cells and CD4＋CD25＋ Treg cells decrease in an age-dependent manner. We show that treatment with α-galactosyiceramide increases the size of the CD4＋CD25＋ Treg cell compartment in NOD mice, and augments the expression of forkhead/winged helix transcription factor and the potency of CD4＋CD25＋ Treg cells to inhibit proliferation of CD4＋CD25＋ T cells. Our data indicate that NKT cells and CD4＋CD25＋ Treg cells might cooperate in the prevention of autoimmune diabetes in NOD mice treated with α-galactosyiceramide. Induced cooperation of NKT cells and CD4＋CD25＋ Treg cells could serve as a strategy to treat human autoimmune disease, such as type 1 diabetes.CDld-restricted natural killer T （NKT） cells and CD4＋CD25＋ regulatory T （Treg） cells are two thymus-derived subsets of regulatory T cells that play an important role in the maintenance of self-tolerance. Yet the functional changes of the two subsets of regulatory T cells in the development of diabetes in non-obese diabetic （NOD） mice remain unclear, and how NKT cells and CD4＋CD25＋ Treg cells cooperate functionally in the regulation of autoimmune diabetes is also uncertain. We provide evidence that in NOD mice, an animal model of human type 1 diabetes, the functions of both NKT cells and CD4＋CD25＋ Treg cells decrease in an age-dependent manner. We show that treatment with α-galactosyiceramide increases the size of the CD4＋CD25＋ Treg cell compartment in NOD mice, and augments the expression of forkhead/winged helix transcription factor and the potency of CD4＋CD25＋ Treg cells to inhibit proliferation of CD4＋CD25＋ T cells. Our data indicate that NKT cells and CD4＋CD25＋ Treg cells might cooperate in the prevention of autoimmune diabetes in NOD mice treated with α-galactosyiceramide. Induced cooperation of NKT cells and CD4＋CD25＋ Treg cells could serve as a strategy to treat human autoimmune disease, such as type 1 diabetes.

关 键 词：invariant NKT cell TREG FOXP3 type 1 diabetes α-galactosylceramide 

分 类 号：R587.1[医药卫生—内分泌] Q1[医药卫生—内科学]