Activated iNKT cells promote memory CD8+ T cell differentiation during viral infection.
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.
Division of Biology and Medicine, Department of Molecular Microbiology and Immunology and Graduate Program in Pathobiology, Brown University, Providence, Rhode Island, United States of America.
Emma C
EC
Reilly
Elizabeth A
EA
Thompson
Sandrine
S
Aspeslagh
Jack R
JR
Wands
Dirk
D
Elewaut
Laurent
L
Brossay
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology*; D016207:Cytokines / Q000097:blood; D003586:Cytomegalovirus Infections / Q000276:immunology*; D005434:Flow Cytometry; D005699:Galactosylceramides / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology*; D007156:Immunologic Memory / Q000276:immunology; D007249:Inflammation / Q000276:immunology* / Q000821:virology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D055611:Natural Killer T-Cells / Q000276:immunology*; D018709:Statistics, Nonparametric
D000276:Adjuvants, Immunologic; D016207:Cytokines; D005699:Galactosylceramides; C493154:alpha-galactosylceramide