Characterization of the immature dendritic cells and cytotoxic cells both expanded after activation of invariant NKT cells with α-galactosylceramide in vivo

2008 ◽  
Vol 369 (2) ◽  
pp. 485-492 ◽  
Author(s):  
Yuki Tamura ◽  
Annabelle Teng ◽  
Risa Nozawa ◽  
Yukiko Takamoto-Matsui ◽  
Yasuyuki Ishii
Keyword(s):  
Dendritic Cells ◽  
Nkt Cells ◽  
Cytotoxic Cells ◽  
Invariant Nkt Cells ◽  
Immature Dendritic Cells

scholarly journals Invariant NKT cells with chimeric antigen receptor provide a novel platform for safe and effective cancer immunotherapy

Blood ◽  
2014 ◽  
Vol 124 (18) ◽  
pp. 2824-2833 ◽  
Author(s):  
Andras Heczey ◽  
Daofeng Liu ◽  
Gengwen Tian ◽  
Amy N. Courtney ◽  
Jie Wei ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Chimeric Antigen Receptor ◽  
Nkt Cells ◽  
T Helper ◽  
T Helper 1 ◽  
Graft Versus Host ◽  
Invariant Nkt Cells ◽  
In Vivo Antitumor Activity ◽  
Key Points

Key Points GD2-specific CAR renders NKT cells cytotoxic against NB cells and results in potent in vivo antitumor activity without graft-versus-host disease. The 4-1BB-containing CAR constructs induce T helper 1–like polarization in NKT cells.

scholarly journals Sustained expansion of NKT cells and antigen-specific T cells after injection of α-galactosyl-ceramide loaded mature dendritic cells in cancer patients

2005 ◽  
Vol 201 (9) ◽  
pp. 1503-1517 ◽  
Author(s):  
David H. Chang ◽  
Keren Osman ◽  
John Connolly ◽  
Anjli Kukreja ◽  
Joseph Krasovsky ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Advanced Cancer ◽  
Serum Levels ◽  
Nkt Cells ◽  
Interleukin 12 ◽  
Cell Immunity ◽  
Galactosyl Ceramide ◽  
Inducible Protein

Natural killer T (NKT) cells are distinct glycolipid reactive innate lymphocytes that are implicated in the resistance to pathogens and tumors. Earlier attempts to mobilize NKT cells, specifically, in vivo in humans met with limited success. Here, we evaluated intravenous injection of monocyte-derived mature DCs that were loaded with a synthetic NKT cell ligand, α-galactosyl-ceramide (α-GalCer; KRN-7000) in five patients who had advanced cancer. Injection of α-GalCer–pulsed, but not unpulsed, dendritic cells (DCs) led to >100-fold expansion of several subsets of NKT cells in all patients; these could be detected for up to 6 mo after vaccination. NKT activation was associated with an increase in serum levels of interleukin-12 p40 and IFN-γ inducible protein-10. In addition, there was an increase in memory CD8+ T cells specific for cytomegalovirus in vivo in response to α-GalCer–loaded DCs, but not unpulsed DCs. These data demonstrate the feasibility of sustained expansion of NKT cells in vivo in humans, including patients who have advanced cancer, and suggest that NKT activation might help to boost adaptive T cell immunity in vivo.

scholarly journals Distinct subsets of human invariant NKT cells differentially regulate T helper responsesvia dendritic cells

2008 ◽  
Vol 38 (4) ◽  
pp. 1012-1023 ◽  
Author(s):  
Tian-Yi Liu ◽  
Yasushi Uemura ◽  
Motoharu Suzuki ◽  
Yayoi Narita ◽  
Shinya Hirata ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Nkt Cells ◽  
T Helper ◽  
Invariant Nkt Cells

scholarly journals Antigen-Specific Cytotoxicity by Invariant NKT Cells In Vivo Is CD95/CD178-Dependent and Is Correlated with Antigenic Potency

2010 ◽  
Vol 185 (5) ◽  
pp. 2721-2729 ◽  
Author(s):  
Gerhard Wingender ◽  
Philippe Krebs ◽  
Bruce Beutler ◽  
Mitchell Kronenberg
Keyword(s):  
Nkt Cells ◽  
Invariant Nkt Cells ◽  
Specific Cytotoxicity

scholarly journals The Natural Killer T (NKT) Cell Ligand α-Galactosylceramide Demonstrates Its Immunopotentiating Effect by Inducing Interleukin (IL)-12 Production by Dendritic Cells and IL-12 Receptor Expression on NKT Cells

1999 ◽  
Vol 189 (7) ◽  
pp. 1121-1128 ◽  
Author(s):  
Hidemitsu Kitamura ◽  
Kenji Iwakabe ◽  
Takashi Yahata ◽  
Shin-ichiro Nishimura ◽  
Akio Ohta ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Natural Killer ◽  
Cd40 Ligand ◽  
Nkt Cells ◽  
Receptor Expression ◽  
Antitumor Activities ◽  
Nkt Cell ◽  
Ifn Γ ◽  
Natural Killer T

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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