The DOI matches its Crossref record; 57 of the 57 references it cites were found in a registry or an index.
Human NKT Cells Mediate Antitumor Cytotoxicity Directly by Recognizing Target Cell CD1d with Bound Ligand or Indirectly by Producing IL-2 to Activate NK Cells
Abstract
α-Galactosylceramide (αGalCer) 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/αGalCer tetrameric complexes were used to obtain highly purified human αGalCer-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 αGalCer. 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 αGalCer. Upon human CD1d/αGalCer 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-γ. 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.
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Cites
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Cited by
Lynch, L., O'Shea, D., Winter, D. C., Geoghegan, J., Doherty, D. G., & O'Farrelly, C. (2009) · European Journal of Immunology · doi:10.1002/eji.200939349 · Cited by 257
Healy, C., Munoz-Wolf, N., Strydom, J., Faherty, L., Williams, N. C., Kenny, S., Donnelly, S. C., & Cloonan, S. M. (2021) · Respiratory Research · doi:10.1186/s12931-021-01722-y · Cited by 78
Metadata
- Authors
- Metelitsa, L. S., Naidenko, O. V., Kant, A., Wu, H.-W., Loza, M. J., Perussia, B., Kronenberg, M., & Seeger, R. C.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2001-09
- Volume
- 167
- Issue
- 6
- Pages
- 3114-3122
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2114565147
- Cited by
- 355
- References
- 57
- FWCI
- 5.72
- Type
- journal article
- Language
- en
- Open access
- closed
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- The paper
- Metelitsa, L. S., Naidenko, O. V., Kant, A., Wu, H.-W., Loza, M. J., Perussia, B., Kronenberg, M., & Seeger, R. C. (2001). Human NKT Cells Mediate Antitumor Cytotoxicity Directly by Recognizing Target Cell CD1d with Bound Ligand or Indirectly by Producing IL-2 to Activate NK Cells. The Journal of Immunology. https://doi.org/10.4049/jimmunol.167.6.3114
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