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Publication : Impact of bacteria on the phenotype, functions, and therapeutic activities of invariant NKT cells in mice.

First Author  Kim S Year  2008
Journal  J Clin Invest Volume  118
Issue  6 Pages  2301-15
PubMed ID  18451996 Mgi Jnum  J:137699
Mgi Id  MGI:3801539 Doi  10.1172/JCI33071
Citation  Kim S, et al. (2008) Impact of bacteria on the phenotype, functions, and therapeutic activities of invariant NKT cells in mice. J Clin Invest 118(6):2301-15
abstractText  Invariant NKT (iNKT) cells are innate-like lymphocytes that recognize glycolipid antigens in the context of the MHC class I-like antigen-presenting molecule CD1d. In vivo activation of mouse iNKT cells with the glycolipid alpha-galactosylceramide (alpha-GalCer) results in the acquisition of a hyporesponsive (anergic) phenotype by these cells. Because iNKT cells can become activated in the context of infectious agents, here we evaluated whether iNKT cell activation by microorganisms can influence subsequent responses of these cells to glycolipid antigen stimulation. We found that mouse iNKT cells activated in vivo by multiple bacterial microorganisms, or by bacterial LPS or flagellin, became unresponsive to subsequent activation with alpha-GalCer. This hyporesponsive phenotype of iNKT cells required IL-12 expression and was associated with changes in the surface phenotype of these cells, reduced severity of concanavalin A-induced hepatitis, and alterations in the therapeutic activities of alpha-GalCer. These findings may have important implications for the development of iNKT cell-based therapies.
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