Clinical application of NKT cell assays to the prediction of type 1 diabetes.

Abstract

Type 1 diabetes is a disease characterised by disturbed glucose homeostasis, which results from autoimmune destruction of the insulin-producing beta cells in the pancreas. The autoimmune attack, while not yet fully characterised, exhibits components of both mis-targeting and failed tolerance induction. The involvement of non-classical lymphocytes in the induction and maintenance of peripheral tolerance has recently been recognised and natural killer T (NKT) cells appear to play such a role. NKT cells are a subset of T cells that are distinct in being able to produce cytokines such as IL-4 and IFN-gamma extremely rapidly following activation. These lymphocytes also express some surface receptors, and the lytic activity, characteristic of NK cells. Deficiencies in NKT cells have been identified in animal models of type 1 diabetes, and a causal association has been demonstrated by adoptive transfer experiments in diabetes-prone NOD mice. Preliminary work suggests that a similar relationship may exist between deficiencies in NKT cells and type 1 diabetes in humans, although the techniques reported to date would be difficult to translate to clinical use. Here, we describe methods appropriate to the clinical assessment of NKT cells and discuss the steps required in the assessment and validation of NKT cell assays as a predictor of type 1 diabetes.