1. NKT Cells Are Required for Complete Freund's Adjuvant-Mediated Protection from Autoimmune Diabetes.
- Author
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Lee, I-Fang, van den Elzen, Peter, Tan, Rusung, and Priatel, John J.
- Subjects
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AUTOIMMUNE diseases , *DIABETES , *LABORATORY mice , *MYCOBACTERIUM tuberculosis , *T cells , *BCG vaccines , *PREVENTION , *DISEASES - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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