A Defect in Interleukin 12–induced Activation and Interferon Secretion of Peripheral Natural Killer T Cells in Nonobese Diabetic Mice Suggests New Pathogenic Mechanisms for Insulin-dependent Diabetes Mellitus

Correspondence to: Nora Sarvetnick, Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Rd., La Jolla, CA 92037. Tel:858-784-9066 Fax:858-784-9083 E-mail:noras{at}scripps.edu.

The function of natural killer T (NKT) cells in the immune system has yet to be determined. There is some evidence that their defect is associated with autoimmunity, but it is still unclear how they play a role in regulating the pathogenesis of T cell–mediated autoimmune diseases. It was originally proposed that NKT cells could control autoimmunity by shifting the cytokine profile of autoimmune T cells toward a protective T helper 2 cell (Th2) type. However, it is now clear that the major function of NKT cells in the immune system is not related to their interleukin (IL)-4 secretion. In fact, NKT cells mainly secrete interferon (IFN)- and, activated in the presence of IL-12, acquire a strong inflammatory phenotype and cytotoxic function.

Key Words: natural killer T cells, interferon , interleukin 4, autoimmunity, regulatory cells

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