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

Abstract

The pathogen-host interaction between bacteria and invariant NKT (iNKT) cells is explored in this dissertation. iNKT cells are innate-like lymphocytes that recognize glycolipid antigens in the context of the MHC class I–like antigen-presenting molecule CD1d. The impact of bacterial infection on the phenotype and function of these cells have been carefully dissected in this dissertation, and the results indicate that mouse iNKT cells activated in vivo by multiple bacterial microorganisms, or by bacterial LPS or flagellin, become 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.