Activated iNKT cells promote memory CD8+ T cell differentiation during viral infection.

ABSTRACT: ?-Galactosylceramide (?-GalCer) is the prototypical lipid ligand for invariant NKT cells. Recent studies have proposed that ?-GalCer is an effective adjuvant in vaccination against a range of immune challenges, however its mechanism of action has not been completely elucidated. A variety of delivery methods have been examined including pulsing dendritic cells with ?-GalCer to optimize the potential of ?-GalCer. These methods are currently being used in a variety of clinical trials in patients with advanced cancer but cannot be used in the context of vaccine development against pathogens due to their complexity. Using a simple delivery method, we evaluated ?-GalCer adjuvant properties, using the mouse model for cytomegalovirus (MCMV). We measured several key parameters of the immune response to MCMV, including inflammation, effector, and central memory CD8(+) T cell responses. We found that ?-GalCer injection at the time of the infection decreases viral titers, alters the kinetics of the inflammatory response, and promotes both increased frequencies and numbers of virus-specific memory CD8(+) T cells. Overall, our data suggest that iNKT cell activation by ?-GalCer promotes the development of long-term protective immunity through increased fitness of central memory CD8(+) T cells, as a consequence of reduced inflammation.

SUBMITTER: Reilly EC 

PROVIDER: S-EPMC3359346 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature