[HTML][HTML] Impact of bacteria on the phenotype, functions, and therapeutic activities of invariant NKT cells in mice

S Kim, S Lalani, VV Parekh, TL Vincent… - The Journal of …, 2008 - Am Soc Clin Investig
S Kim, S Lalani, VV Parekh, TL Vincent, L Wu, L Van Kaer
The Journal of clinical investigation, 2008Am Soc Clin Investig
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 α-galactosylceramide (α-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 …
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 α-galactosylceramide (α-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 α-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 α-GalCer. These findings may have important implications for the development of iNKT cell–based therapies.
The Journal of Clinical Investigation