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 ill 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 V alpha 14-J alpha 18 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 ill 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.