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
Weipeng Li
Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China
These authors contributed equally to this work
Search for more papers by this authorFang Ji
Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
These authors contributed equally to this work
Search for more papers by this authorYong Zhang
Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
Search for more papers by this authorYing Wang
Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
Search for more papers by this authorNeng Yang
Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
Search for more papers by this authorHailiang Ge
Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
Search for more papers by this authorCorresponding Author
Fuqing Wang
Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
*Corresponding author: Tel, 86-21-63846590, ext 776632; Fax, 86-21-63846383; E-mail, [email protected]Search for more papers by this authorWeipeng Li
Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China
These authors contributed equally to this work
Search for more papers by this authorFang Ji
Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
These authors contributed equally to this work
Search for more papers by this authorYong Zhang
Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
Search for more papers by this authorYing Wang
Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
Search for more papers by this authorNeng Yang
Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
Search for more papers by this authorHailiang Ge
Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
Search for more papers by this authorCorresponding Author
Fuqing Wang
Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
*Corresponding author: Tel, 86-21-63846590, ext 776632; Fax, 86-21-63846383; E-mail, [email protected]Search for more papers by this authorAbstract
CD1d-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-galactosylceramide 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-galactosylceramide. 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.
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