Activated iNKT Cells Promote Memory CD8(+) T Cell Differentiation during Viral Infection

作者：Reilly Emma C^*; Thompson Elizabeth A; Aspeslagh Sandrine; Wands Jack R; Elewaut Dirk; Brossay Laurent

来源：PLos One, 2012, 7(5): e37991.

DOI：10.1371/journal.pone.0037991

alpha-galactosylceramide (alpha-GalCer) is the prototypical lipid ligand for invariant NKT cells. Recent studies have proposed that alpha-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 alpha-GalCer to optimize the potential of alpha-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 alpha-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 alpha-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 alpha-GalCer promotes the development of long-term protective immunity through increased fitness of central memory CD8(+) T cells, as a consequence of reduced inflammation.

• 出版日期2012-5-23