The natural killer T (NKT) cell ligand α-galactosylceramide demonstrates its immunopotentiating effect by inducing interleukin (IL)-12 production by dendritic cells and …

H Kitamura, K Iwakabe, T Yahata… - The Journal of …, 1999 - rupress.org
H Kitamura, K Iwakabe, T Yahata, S Nishimura, A Ohta, Y Ohmi, M Sato, K Takeda…
The Journal of experimental medicine, 1999rupress.org
The natural killer T (NKT) cell ligand α-galactosylceramide (α-GalCer) exhibits profound
antitumor activities in vivo that resemble interleukin (IL)-12–mediated antitumor activities.
Because of these similarities between the activities of α-GalCer and IL-12, we investigated
the involvement of IL-12 in the activation of NKT cells by α-GalCer. We first established,
using purified subsets of various lymphocyte populations, that α-GalCer selectively activates
NKT cells for production of interferon (IFN)-γ. Production of IFN-γ by NKT cells in response to …
The natural killer T (NKT) cell ligand α-galactosylceramide (α-GalCer) exhibits profound antitumor activities in vivo that resemble interleukin (IL)-12–mediated antitumor activities. Because of these similarities between the activities of α-GalCer and IL-12, we investigated the involvement of IL-12 in the activation of NKT cells by α-GalCer. We first established, using purified subsets of various lymphocyte populations, that α-GalCer selectively activates NKT cells for production of interferon (IFN)-γ. Production of IFN-γ by NKT cells in response to α-GalCer required IL-12 produced by dendritic cells (DCs) and direct contact between NKT cells and DCs through CD40/CD40 ligand interactions. Moreover, α-GalCer strongly induced the expression of IL-12 receptor on NKT cells from wild-type but not CD1−/− or Vα14−/− mice. This effect of α-GalCer required the production of IFN-γ by NKT cells and production of IL-12 by DCs. Finally, we showed that treatment of mice with suboptimal doses of α-GalCer together with suboptimal doses of IL-12 resulted in strongly enhanced natural killing activity and IFN-γ production. Collectively, these findings indicate an important role for DC-produced IL-12 in the activation of NKT cells by α-GalCer and suggest that NKT cells may be able to condition DCs for subsequent immune responses. Our results also suggest a novel approach for immunotherapy of cancer.
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