NKT Cells Inhibit the Onset of Diabetes by Impairing the Development of Pathogenic T Cells Specific for Pancreatic [beta] Cells

To determine the precise regulatory effect of NKT cells on CD4+T cells involved in autoimmune diabetes, we developed an in vivo model in which transferred naive transgenic T cells are stimulated by their antigen in the presence or absence of NKT cells or in the presence of another conventional transgenic αβ T cell. The presence of NKT cells did not block the initial activation and expansion of the CD4+T cells but did inhibit their IL-2 and IFN-γ production and later proliferation, resulting in an anergic phenotype. These CD4+T cells did not induce significant insulitis and were unable to destroy the β cells. Thus, NKT cells prevent αβ CD4 T cell differentiation into effector cells.