Antitumor Cytotoxicity Mediated by Ligand-activated Human Va24 NKT Cells
نویسندگان
چکیده
Human Va24 NKT cells bearing an invariant Va24JaQ antigen receptor, the counterpart of the murine Va14 NKT cells, are activated by the specific ligand, a-galactosylceramide (a-GalCer) in a CD1d-dependent manner. Here, we demonstrate that the a-GalCer-activated Va24 NKT cells exert a potent perforin-dependent cytotoxic activity against a wide variety of human tumor cell lines. In addition, we demonstrate that Va24 NKT cells and dendritic cells (DCs) from melanoma patients are functionally normal, even in the tumor-bearing status. The potential use of a-GalCer-activated Va24 NKT cells and/or DCs from patients for cancer immunotherapy is discussed.
منابع مشابه
Analysis of Human Va24 CD4 NKT Cells Activated by a-Glycosylceramide-Pulsed Monocyte-Derived Dendritic Cells
Human Va24 NKT cells with an invariant TCR (Va24-JaQ) have been shown to be specifically activated by synthetic glycolipids such as a-galactosylceramide and a-glucosylceramide in a CD1d-restricted and Va24 TCR-mediated manner. We recently characterized Va24 CD4 CD8 double negative (DN) NKT cells using a-galactosylceramide-pulsed monocyte-derived dendritic cells. Here, we compare Va24 CD4 NKT ce...
متن کاملNatural killer-like nonspecific tumor cell lysis mediated by specific ligand-activated Valpha14 NKT cells.
We have recently identified alpha-galactosylceramide (alpha-GalCer) as a specific ligand for an invariant Valpha14/Vbeta8.2 T cell receptor exclusively expressed on the majority of Valpha14 NKT cells, a novel subset of lymphocytes. Here, we report that alpha-GalCer selectively activates Valpha14 NKT cells resulting in prevention of tumor metastasis. The effector mechanisms of the ligand-activat...
متن کاملHuman NKT cells mediate antitumor cytotoxicity directly by recognizing target cell CD1d with bound ligand or indirectly by producing IL-2 to activate NK cells.
alpha-Galactosylceramide (alphaGalCer) 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/alphaGalCer tetrameric complexes were used to obtain highly purified human alphaGalCer-reactive NKT cell lines (>99%), and the mechanisms of NKT cell cyt...
متن کاملAge-associated augmentation of the synthetic ligand- mediated function of mouse NK1.1 ag(+) T cells: their cytokine production and hepatotoxicity in vivo and in vitro.
We recently reported that the direct antitumor effectors in the liver induced by alpha-galactosylceramide (alpha-GalCer) are NK cells that are activated by the IFN-gamma produced from NK1.1 Ag(+) T cells (NKT cells) specifically stimulated with alpha-GalCer, whereas NKT cells cause hepatocyte injury through the Fas-Fas ligand pathway. In the present study, we investigated how mouse age affects ...
متن کامل