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

PLoS One. 2012;7(5):e37991. doi: 10.1371/journal.pone.0037991. Epub 2012 May 23.

Abstract

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

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adjuvants, Immunologic / pharmacology
  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Differentiation / immunology*
  • Cytokines / blood
  • Cytomegalovirus Infections / immunology*
  • Flow Cytometry
  • Galactosylceramides / administration & dosage
  • Galactosylceramides / immunology
  • Galactosylceramides / pharmacology*
  • Immunologic Memory / immunology
  • Inflammation / immunology*
  • Inflammation / virology
  • Lymphocyte Activation / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Natural Killer T-Cells / immunology*
  • Statistics, Nonparametric

Substances

  • Adjuvants, Immunologic
  • Cytokines
  • Galactosylceramides
  • alpha-galactosylceramide