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[Cancer Research 63, 4101-4106, July 15, 2003]
© 2003 American Association for Cancer Research

Immunology

Polarization of V{alpha}24+ Vß11+ Natural Killer T Cells of Healthy Volunteers and Cancer Patients Using {alpha}-Galactosylceramide-loaded and Environmentally Instructed Dendritic Cells1

Hans J. J. van der Vliet, Johan W. Molling, Nobusuke Nishi, Allan J. Masterson, Wendy Kölgen, Steven A. Porcelli, Alfons J. M. van den Eertwegh, B. Mary E. von Blomberg, Herbert M. Pinedo, Giuseppe Giaccone and Rik J. Scheper2

Departments of Medical Oncology [H. J. J. v. d. V., N. N., A. J. M., W. K., A. J. M. v. d. E., H. M. P., G. G., R. J. S.] and Pathology [H. J. J. v. d. V., A. J. M., W. K., B. M. E. v. B., R. J. S.], Vrije Universiteit Medisch Centrum, Amsterdam, the Netherlands; Pharmaceutical Research Laboratory, Kirin Brewery Co., Ltd., Gunma, 370-1295, Japan [N. N.]; and Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461 [S. A. P.]

CD1d-restricted natural killer T (NKT) cells play important regulatory roles in various immune responses. NKT cell-derived T helper (Th) 1 cytokines are important in the induction of antitumor immune responses in mice. Because the CD1d-restricted V{alpha}24+ Vß11+ NKT cell population in cancer patients is decreased both in size and in its capacity to secrete IFN-{gamma}, therapeutic strategies based on reconstitution of type 1 polarized V{alpha}24+ Vß11+ NKT cells merit additional investigation. Here, we report the simultaneous strong expansion and type 1 polarization of human invariant V{alpha}24+ Vß11+ NKT cells using {alpha}-galactosylceramide-loaded type 1 dendritic cells and interleukin 15. Type 1 polarized V{alpha}24+ Vß11+ NKT cells produced high levels of IFN-{gamma}, tumor necrosis factor {alpha}, and granulocyte macrophage colony-stimulating factor, and induced strong cytotoxicity in Jurkat cells in an {alpha}-galactosylceramide-dependent manner. Importantly, the cytokine profile of V{alpha}24+ Vß11+ NKT cells that were initially expanded under Th2 polarizing conditions could be reversed to a Th1 cytokine profile, indicating the plasticity of the cytokine profile of the human adult V{alpha}24+ Vß11+ NKT cell population.




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Copyright © 2003 by the American Association for Cancer Research.