title: NKT cells are required for complete Freund's adjuvant-mediated protection from autoimmune diabetes.
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.
authors.affiliation: Child & Family Research Institute, Immunity in Health and Disease, BC Children's Hospital, Vancouver, British Columbia V5Z 4H4, Canada.
authors.forename: I-Fang
authors.initials: IF
authors.lastname: Lee
authors.forename: Peter
authors.initials: P
authors.lastname: van den Elzen
authors.forename: Rusung
authors.initials: R
authors.lastname: Tan
authors.forename: John J
authors.initials: JJ
authors.lastname: Priatel
mesh_terms: D000818:Animals; D002469:Cell Separation; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D005620:Freund's Adjuvant / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology*
chemical_list: D005620:Freund's Adjuvant