Role of regulatory invariant CD1d-restricted natural killer T-cells in protection against type 1 diabetes.
Invariant CD1d-restricted natural killer T (iNKT) cells function during innate and adaptive immune responses. A functional and numerical deficiency of iNKT cells is well documented in both nonobese diabetic (NOD) mice and humans with autoimmune type 1 diabetes (T1D). Restoring the numerical and/or functional deficiency of iNKT cells in NOD mice by either treatment with alpha-galactosylceramide, transgenic induction of Valpha14-Jalpha18 expression, or transgenic expression of CD1d in NOD islets under the control of the human insulin promoter confers protection from T1D in these mice. Recently, considerable progress has been made in understanding the developmental and functional activities of iNKT cells. In this review, we discuss the role of iNKT cell deficiency and defective development in the onset of T1D in NOD mice and the different protective mechanisms known to restore these defects.
Hussain
Shabbir
S
Autoimmunity/Diabetes Group, Robarts Research Institute, 1400 Western Road, London, Ontario N6G 2V4, Canada.
Wagner
Melany
M
Ly
Dalam
D
Delovitch
Terry L
TL
D000818:Animals; D018949:Antigens, CD1 / Q000378:metabolism*; D055610:Antigens, CD1d; D016207:Cytokines / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D006801:Humans; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D016131:Lymphocyte Subsets / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D011401:Promoter Regions, Genetic; D018418:Th2 Cells / Q000276:immunology*
D018949:Antigens, CD1; D055610:Antigens, CD1d; C526877:CD1D protein, human; D016207:Cytokines; D007328:Insulin