The preventive role of type 2 NKT cells in the development of type 1 diabetes.

In the last two decades, natural killer T (NKT) cells have emerged as an important factor in preventingtype 1 diabetes (T1D) when investigated in the experimental non-obese diabetic (NOD) mouse model. Sofar, investigations have largely focused on type 1 NKT cells with invariant T-cell receptors, whereas therole of type 2 NKT cells with diverse T-cell receptors is less well understood. However, there have beenseveral findings which indicate that in fact type 2 NKT cells may regulate the progression of type 1 diabe-tes in NOD mice, including a fraction of these cells which recognize b-cell-enriched sulfatide. Therefore,the focus for this review is to present the current evidence of the effect of type 2 NKT cells on the develop-ment of T1D. In general, there is still uncertainty surrounding the mechanism of activation and functionof NKT cells. Here, we present two models of the effector mechanisms, respectively, Th1/Th2 polarizationand the induction of tolerogenic dendritic cells (DC). In conclusion, this review points to the importanceof immunoregulation by type 2 NKT cells in preventing the development of T1D and highlights the induc-tion of tolerogenic DC as a likely mechanism. The possible therapeutic role of type 1 and type 2 NKT cellsare evaluated and future experiments concerning type 2 NKT cells and T1D are proposed.Key words: Natural killer T cell; sulfatide; beta cell; diabetes; prevention.Carl-Henrik Brogren, The Bartholin Institute, Rigshospitalet, Ole Maaloesvej 5, DK-2200 Copenhagen N,Denmark. e-mail: henrik@brogren.dk