| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
Division of Hematology-Oncology, Department of Pediatrics, Children’s Hospital Los Angeles and Keck School of Medicine, University of Southern California, Los Angeles, CA 90027;
Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121; and
Kimmel Cancer Center, Department of Microbiology and Immunology, Jefferson Medical College, Philadelphia, PA 19107
-Galactosylceramide (GalCer) stimulates NKT cells and has
antitumor activity in mice. Murine NKT cells may directly kill tumor
cells and induce NK cell cytotoxicity, but the mechanisms are not well
defined. Newly developed human CD1d/GalCer tetrameric complexes were
used to obtain highly purified human GalCer-reactive NKT cell lines
(>99%), and the mechanisms of NKT cell cytotoxicity and activation of
NK cells were investigated. Human NKT cells were cytotoxic against
CD1d- neuroblastoma cells only when they were rendered
CD1d+ by transfection and pulsed with GalCer. Four other
CD1d- tumor cell lines of diverse origin were resistant to
NKT cells, whereas Jurkat and U937 leukemia cell lines, which are
constitutively CD1d+, were killed. Killing of the latter
was greatly augmented in the presence of GalCer. Upon human
CD1d/GalCer recognition, NKT cells induced potent cytotoxicity of NK
cells against CD1d- neuroblastoma cell lines that were not
killed directly by NKT cells. NK cell activation depended upon NKT cell
production of IL-2, and was enhanced by secretion of IFN-
. These
data demonstrate that cytotoxicity of human NKT cells can be CD1d and
ligand dependent, and that TCR-stimulated NKT cells produce IL-2 that
is required to induce NK cell cytotoxicity. Thus, NKT cells can mediate
potent antitumor activity both directly by targeting CD1d and
indirectly by activating NK cells.
This article has been cited by other articles:
|
|
 |
|
  K. Azakami, T. Sato, N. Araya, A. Utsunomiya, R. Kubota, K. Suzuki, D. Hasegawa, T. Izumi, H. Fujita, S. Aratani, et al. Severe loss of invariant NKT cells exhibiting anti-HTLV-1 activity in patients with HTLV-1-associated disorders Blood, October 8, 2009; 114(15): 3208 - 3215. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Bricard, V. Cesson, E. Devevre, H. Bouzourene, C. Barbey, N. Rufer, J. S. Im, P. M. Alves, O. Martinet, N. Halkic, et al. Enrichment of Human CD4+ V{alpha}24/V{beta}11 Invariant NKT Cells in Intrahepatic Malignant Tumors J. Immunol., April 15, 2009; 182(8): 5140 - 5151. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. K. Hu, F. Venet, D. S. Heffernan, Y. L. Wang, B. Horner, X. Huang, C.-S. Chung, S. H. Gregory, and A. Ayala The Role of Hepatic Invariant NKT Cells in Systemic/Local Inflammation and Mortality during Polymicrobial Septic Shock J. Immunol., February 15, 2009; 182(4): 2467 - 2475. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-C. Huang, S.-W. Hung, T.-R. Jan, K.-W. Liao, C.-H. Cheng, Y.-S. Wang, and R.-M. Chu CD5-low expression lymphocytes in canine peripheral blood show characteristics of natural killer cells J. Leukoc. Biol., December 1, 2008; 84(6): 1501 - 1510. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Song, H. J.J. van der Vliet, Y.-T. Tai, R. Prabhala, R. Wang, K. Podar, L. Catley, M. A. Shammas, K. C. Anderson, S. P. Balk, et al. Generation of Antitumor Invariant Natural Killer T Cell Lines in Multiple Myeloma and Promotion of Their Functions via Lenalidomide: A Strategy for Immunotherapy Clin. Cancer Res., November 1, 2008; 14(21): 6955 - 6962. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ozeki and J. E. Shively Differential cell fates induced by all-trans retinoic acid-treated HL-60 human leukemia cells J. Leukoc. Biol., September 1, 2008; 84(3): 769 - 779. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Moreno, J. W. Molling, S. von Mensdorff-Pouilly, R. H. M. Verheijen, E. Hooijberg, D. Kramer, A. W. Reurs, A. J. M. van den Eertwegh, B. M. E. von Blomberg, R. J. Scheper, et al. IFN-{gamma}-Producing Human Invariant NKT Cells Promote Tumor-Associated Antigen-Specific Cytotoxic T Cell Responses J. Immunol., August 15, 2008; 181(4): 2446 - 2454. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Chen, X. Wang, G. S. Besra, and J. E. Gumperz Modulation of CD1d-restricted NKT cell responses by CD4 J. Leukoc. Biol., December 1, 2007; 82(6): 1455 - 1465. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. W. Molling, J. A.E. Langius, J. A. Langendijk, C. R. Leemans, H. J. Bontkes, H. J.J. van der Vliet, B. M. E. von Blomberg, R. J. Scheper, and A. J.M. van den Eertwegh Low Levels of Circulating Invariant Natural Killer T Cells Predict Poor Clinical Outcome in Patients With Head and Neck Squamous Cell Carcinoma J. Clin. Oncol., March 1, 2007; 25(7): 862 - 868. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Raftery, F. Winau, S. H. E. Kaufmann, U. E. Schaible, and G. Schonrich CD1 Antigen Presentation by Human Dendritic Cells as a Target for Herpes Simplex Virus Immune Evasion J. Immunol., November 1, 2006; 177(9): 6207 - 6214. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. J.J. van der Vliet, S. P. Balk, and M. A. Exley Natural Killer T Cell-Based Cancer Immunotherapy. Clin. Cancer Res., October 15, 2006; 12(20): 5921 - 5923. [Full Text] [PDF]
|
|
|
|
|
|
K. Shimizu, M. Hidaka, N. Kadowaki, N. Makita, N. Konishi, K. Fujimoto, T. Uchiyama, F. Kawano, M. Taniguchi, and S.-i. Fujii Evaluation of the Function of Human Invariant NKT Cells from Cancer Patients Using {alpha}-Galactosylceramide-Loaded Murine Dendritic Cells. J. Immunol., September 1, 2006; 177(5): 3484 - 3492. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Lin, M. Nieda, J. F. Hutton, V. Rozenkov, and A. J. Nicol Comparative gene expression analysis of NKT cell subpopulations J. Leukoc. Biol., July 1, 2006; 80(1): 164 - 173. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Osada, M. A. Morse, H. K. Lyerly, and T. M. Clay Ex vivo expanded human CD4+ regulatory NKT cells suppress expansion of tumor antigen-specific CTLs Int. Immunol., September 1, 2005; 17(9): 1143 - 1155. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. K. Dougan, A. Salas, P. Rava, A. Agyemang, A. Kaser, J. Morrison, A. Khurana, M. Kronenberg, C. Johnson, M. Exley, et al. Microsomal triglyceride transfer protein lipidation and control of CD1d on antigen-presenting cells J. Exp. Med., August 15, 2005; 202(4): 529 - 539. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. H. Chang, K. Osman, J. Connolly, A. Kukreja, J. Krasovsky, M. Pack, A. Hutchinson, M. Geller, N. Liu, R. Annable, et al. Sustained expansion of NKT cells and antigen-specific T cells after injection of {alpha}-galactosyl-ceramide loaded mature dendritic cells in cancer patients J. Exp. Med., May 2, 2005; 201(9): 1503 - 1517. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Crough, M. Nieda, and A. J. Nicol Granulocyte Colony-Stimulating Factor Modulates {alpha}-Galactosylceramide-Responsive Human V{alpha}24+V{beta}11+ NKT Cells J. Immunol., October 15, 2004; 173(8): 4960 - 4966. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Durante-Mangoni, R. Wang, A. Shaulov, Q. He, I. Nasser, N. Afdhal, M. J. Koziel, and M. A. Exley Hepatic CD1d Expression in Hepatitis C Virus Infection and Recognition by Resident Proinflammatory CD1d-Reactive T Cells J. Immunol., August 1, 2004; 173(3): 2159 - 2166. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. S. Metelitsa, H.-W. Wu, H. Wang, Y. Yang, Z. Warsi, S. Asgharzadeh, S. Groshen, S. B. Wilson, and R. C. Seeger Natural Killer T Cells Infiltrate Neuroblastomas Expressing the Chemokine CCL2 J. Exp. Med., May 3, 2004; 199(9): 1213 - 1221. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Nieda, M. Okai, A. Tazbirkova, H. Lin, A. Yamaura, K. Ide, R. Abraham, T. Juji, D. J. Macfarlane, and A. J. Nicol Therapeutic activation of V{alpha}24+V{beta}11+ NKT cells in human subjects results in highly coordinated secondary activation of acquired and innate immunity Blood, January 15, 2004; 103(2): 383 - 389. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. M. Esteban, T. Tsoutsman, M. A. Jordan, D. Roach, L. D. Poulton, A. Brooks, O. V. Naidenko, S. Sidobre, D. I. Godfrey, and A. G. Baxter Genetic Control of NKT Cell Numbers Maps to Major Diabetes and Lupus Loci J. Immunol., September 15, 2003; 171(6): 2873 - 2878. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. N. Baxevanis, A. D. Gritzapis, and M. Papamichail In Vivo Antitumor Activity of NKT Cells Activated by the Combination of IL-12 and IL-18 J. Immunol., September 15, 2003; 171(6): 2953 - 2959. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kenna, L. G. Mason, S. A. Porcelli, Y. Koezuka, J. E. Hegarty, C. O'Farrelly, and D. G. Doherty NKT Cells from Normal and Tumor-Bearing Human Livers Are Phenotypically and Functionally Distinct from Murine NKT Cells J. Immunol., August 15, 2003; 171(4): 1775 - 1779. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. J. J. van der Vliet, J. W. Molling, N. Nishi, A. J. Masterson, W. Kolgen, S. A. Porcelli, A. J. M. van den Eertwegh, B. M. E. von Blomberg, H. M. Pinedo, G. Giaccone, et al. Polarization of V{alpha}24+ V{beta}11+ Natural Killer T Cells of Healthy Volunteers and Cancer Patients Using {alpha}-Galactosylceramide-loaded and Environmentally Instructed Dendritic Cells Cancer Res., July 15, 2003; 63(14): 4101 - 4106. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. V. Dhodapkar, M. D. Geller, D. H. Chang, K. Shimizu, S.-I. Fujii, K. M. Dhodapkar, and J. Krasovsky A Reversible Defect in Natural Killer T Cell Function Characterizes the Progression of Premalignant to Malignant Multiple Myeloma J. Exp. Med., June 16, 2003; 197(12): 1667 - 1676. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Gansert, V. Kiebler, M. Engele, F. Wittke, M. Rollinghoff, A. M. Krensky, S. A. Porcelli, R. L. Modlin, and S. Stenger Human NKT Cells Express Granulysin and Exhibit Antimycobacterial Activity J. Immunol., March 15, 2003; 170(6): 3154 - 3161. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Miyahira, M. Katae, K. Takeda, H. Yagita, K. Okumura, S. Kobayashi, T. Takeuchi, T. Kamiyama, Y. Fukuchi, and T. Aoki Activation of Natural Killer T Cells by {alpha}-Galactosylceramide Impairs DNA Vaccine-Induced Protective Immunity against Trypanosoma cruzi Infect. Immun., March 1, 2003; 71(3): 1234 - 1241. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. L. H. van Dommelen, H. A. Tabarias, M. J. Smyth, and M. A. Degli-Esposti Activation of Natural Killer (NK) T Cells during Murine Cytomegalovirus Infection Enhances the Antiviral Response Mediated by NK Cells J. Virol., February 1, 2003; 77(3): 1877 - 1884. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Giaccone, C. J. A. Punt, Y. Ando, R. Ruijter, N. Nishi, M. Peters, B. M. E. von Blomberg, R. J. Scheper, H. J. J. van der Vliet, A. J. M. van den Eertwegh, et al. A Phase I Study of the Natural Killer T-Cell Ligand {alpha}-Galactosylceramide (KRN7000) in Patients with Solid Tumors Clin. Cancer Res., December 1, 2002; 8(12): 3702 - 3709. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Loza and B. Perussia Peripheral Immature CD2-/low T Cell Development from Type 2 to Type 1 Cytokine Production J. Immunol., September 15, 2002; 169(6): 3061 - 3068. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Takahashi, S. Chiba, M. Nieda, T. Azuma, S. Ishihara, Y. Shibata, T. Juji, and H. Hirai Cutting Edge: Analysis of Human V{alpha}24+CD8+ NK T Cells Activated by {alpha}-Galactosylceramide-Pulsed Monocyte-Derived Dendritic Cells J. Immunol., April 1, 2002; 168(7): 3140 - 3144. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Exley, Q. He, O. Cheng, R.-J. Wang, C. P. Cheney, S. P. Balk, and M. J. Koziel Cutting Edge: Compartmentalization of Th1-Like Noninvariant CD1d-Reactive T Cells in Hepatitis C Virus-Infected Liver J. Immunol., February 15, 2002; 168(4): 1519 - 1523. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
