Cutting edge: Cross-talk between cells of the innate immune system: NKT cells rapidly activate NK cells.
alpha-Galactosylceramide (alpha-GalCer) is a glycolipid with potent antitumor properties that binds to CD1d molecules and activates mouse Valpha14 and human Valpha24 NKT cells. Surprisingly, we found that, as early as 90 min after alpha-GalCer injection in vivo, NK cells also displayed considerable signs of activation, including IFN-gamma production and CD69 induction. NK activation was not observed in RAG- or CD1-deficient mice, and it was decreased by pretreatment with anti-IFN-gamma Abs, suggesting that, despite its rapid induction, it was a secondary event that depended on IFN-gamma release by NKT cells. At later time points, B cells and CD8 T cells also began to express CD69. These findings identify a high-speed communication network between the innate and adaptive immune systems in vivo that is initiated upon NKT cell activation. They also suggest that the antitumor effects of alpha-GalCer result from the sequential recruitment of distinct innate and adaptive effector lymphocytes.
Carnaud
C
C
Department of Molecular Biology, Princeton University, NJ 08544, USA. carnaud@infobiogen.fr
Lee
D
D
Donnars
O
O
Park
S H
SH
Beavis
A
A
Koezuka
Y
Y
Bendelac
A
A
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D018949:Antigens, CD1 / Q000502:physiology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D002450:Cell Communication / Q000276:immunology*; D005699:Galactosylceramides / Q000008:administration & dosage / Q000276:immunology; D007113:Immunity, Innate; D007275:Injections, Intravenous; D007371:Interferon-gamma / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D015398:Signal Transduction / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D000099192:CD69 Antigens
D015703:Antigens, CD; D018949:Antigens, CD1; D000945:Antigens, Differentiation, T-Lymphocyte; D005699:Galactosylceramides; D007371:Interferon-gamma; D037181:Lectins, C-Type; D000099192:CD69 Antigens