1. NKT cells are required for complete Freund's adjuvant-mediated protection from autoimmune diabetes
- Author
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Rusung Tan, John J. Priatel, Peter van den Elzen, and I-Fang Lee
- Subjects
Immunology ,Freund's Adjuvant ,chemical and pharmacologic phenomena ,Cell Separation ,Lymphocyte Activation ,complex mixtures ,Flow cytometry ,Mycobacterium tuberculosis ,Mice ,Mice, Inbred NOD ,medicine ,Immunology and Allergy ,Animals ,Secretion ,NOD mice ,Mice, Knockout ,biology ,medicine.diagnostic_test ,hemic and immune systems ,Natural killer T cell ,Acquired immune system ,biology.organism_classification ,Flow Cytometry ,In vitro ,Mice, Inbred C57BL ,Diabetes Mellitus, Type 1 ,CD1D ,biology.protein ,Natural Killer T-Cells ,Female - Abstract
Autoimmune diabetes in NOD mice can be prevented by application of Ags derived from Mycobacterium tuberculosis in the form of bacillus Calmette-Guérin or CFA. Disease protection by CFA is associated with a reduction in the numbers of pathogenic β-cell specific, self-reactive CTLs, a phenomenon dependent on the presence and function of NK cells. However, the mechanisms by which NK cells are activated and recruited by heat-killed M. tuberculosis within CFA are unclear. In this study, we report that CFA-mediated NK cell activation and mobilization is dependent on CD1d expression. The administration of M. tuberculosis from CFA results in rapid NKT cell activation and IFN-γ secretion both in vitro and in vivo. CFA-induced NKT cell activation is intact in MyD88−/− mice suggesting that the mechanism is independent of TLR signaling. Furthermore, CD1d expression was found to be essential for both M. tuberculosis-triggered NKT cell activation and CFA-mediated protection of NOD mice from diabetes. Collectively, these findings reveal hitherto previously unidentified roles for NKT cells in the adjuvant-promoting effects of CFA on innate and adaptive immunity.
- Published
- 2011