Fig. 3.

Possible influence of CD1d expression and natural killer T (NKT) cells during the autoimmune reactions preceding diabetes in non-obese diabetic (NOD) mice. (a) At around 2 weeks of age β-cell antigens from apoptotic cells are acquired by antigen-presenting cells and transported from the pancreas to the pancreatic lymph nodes [5] (b). This leads to the activation of autoreactive T cells at this site (c). Bone marrow derived dendritic cells (DC) from NOD mice have reduced levels of CD1d [81], suggesting that inappropriate display of CD1d on DC in NOD mice may contribute to reduced NKT cell activation. Administration of α-galactocylceramide (αGalCer) results in the accumulation of iNKT cells and tolerogenic DC selectively in the pancreatic lymph nodes [68,90], which may create an environment which prevents the development of autoaggressive T cells (c). NKT cells could interfere with the activation and expansion of autoreactive T cells in a cytokine or cell-to-cell contact-dependent manner [95], directly or by modulating DC function. (d) Transgenic over expression of CD1d in the islets reduces diabetes incidence [81]. NKT cells are present in the pancreatic infiltrates in young female NOD mice, and also in male NOD mice at late times [68,91]. Within the pancreas NKT cells may interfere with the expression of β-cell destructive behaviour of autoreactive T cells, or directly kill autoaggressive T cells. (e) The proportion of NKT cells is reduced in the late invasive infiltrates in the pancreas of prediabetic female NOD mice.