The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.
Role of NKG2D signaling in the cytotoxicity of activated and expanded CD8+ T cells
Abstract
Activating and expanding T cells using T-cell receptor (TCR) cross-linking antibodies and interleukin 2 (IL-2) results in potent cytotoxic effector cells capable of recognizing a broad range of malignant cell targets, including autologous leukemic cells. The mechanism of target cell recognition has previously been unknown. Recent studies show that ligation of NKG2D on natural killer (NK) cells directly induces cytotoxicity, whereas on T cells it costimulates TCR signaling. Here we demonstrate that NKG2D expression is up-regulated upon activation and expansion of human CD8+ T cells. Antibody blocking, redirected cytolysis, and small interfering RNA (siRNA) studies using purified CD8+ T cells demonstrate that cytotoxicity against malignant target cells occurs through NKG2D-mediated recognition and signaling and not through the TCR. Activated and expanded CD8+ T cells develop cytotoxicity after 10 to 14 days of culture, coincident with the expression of the adapter protein DAP10. T cells activated and expanded in low (30 U/mL) and high (300 U/mL) concentrations of IL-2 both up-regulated NKG2D expression equally, but only cells cultured in high-dose IL-2 expressed DAP10 and were cytotoxic. Collectively these results establish that NKG2D triggering accounts for the majority of major histocompatibility complex (MHC)–unrestricted cytotoxicity of activated and expanded CD8+ T cells, likely through DAP10-mediated signaling. (Blood. 2004;103: 3065-3072)
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Cites
Activation of NK Cells and T Cells by NKG2D, a Receptor for Stress-Inducible MICA
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Rae1 and H60 ligands of the NKG2D receptor stimulate tumour immunity
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An Activating Immunoreceptor Complex Formed by NKG2D and DAP10
Wu, J., Song, Y., Bakker, A. B. H., Bauer, S., Spies, T., Lanier, L. L., & Phillips, J. H. (1999) · Science · doi:10.1126/science.285.5428.730 · Cited by 1,039
Broad tumor-associated expression and recognition by tumor-derived γδ T cells of MICA and MICB
Groh, V., Rhinehart, R., Secrist, H., Bauer, S., Grabstein, K. H., & Spies, T. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.12.6879 · Cited by 1,028
Groh, V, Bahram, S., Bauer, S., Herman, A., Beauchamp, M., & Spies, T. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.22.12445 · Cited by 1,017
Costimulation of CD8αβ T cells by NKG2D via engagement by MIC induced on virus-infected cells
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Cited by
Up on the tightrope: natural killer cell activation and inhibition
Lanier, L. L. (2008) · Nature Immunology · doi:10.1038/ni1581 · Cited by 1,656
Meresse, B., Chen, Z., Ciszewski, C., Tretiakova, M., Bhagat, G., Krausz, T. N., Raulet, D. H., Lanier, L. L., Groh, V., Spies, T., et al. (2004) · Immunity · doi:10.1016/j.immuni.2004.06.020 · Cited by 855
NKG2D Receptor and Its Ligands in Host Defense
Lanier, L. L. (2015) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-15-0098 · Cited by 599
“Similarly, although expressed on all na€ ve human CD8þ T cells, NKG2D fails to costimulate TCR-induced activation of resting CD8þ T cells (12, 19, 41), and only augments TCRdependent activation after the T cells have been activated and cultured for a period of time in vitro (18, 41, 42).”
BackgroundCD28 extinction in human T cells: altered functions and the program of T‐cell senescence
Vallejo, A. N. (2005) · Immunological Reviews · doi:10.1111/j.0105-2896.2005.00256.x · Cited by 431
Ashiru, O., Boutet, P., Fernández-Messina, L., Agüera-González, S., Skepper, J. N., Valés-Gómez, M., & Reyburn, H. T. (2010) · Cancer Research · doi:10.1158/0008-5472.can-09-1688 · Cited by 421
Metadata
- Authors
- Verneris, M. R., Karami, M., Baker, J., Jayaswal, A., & Negrin, R. S.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2004-04-15
- Volume
- 103
- Issue
- 8
- Pages
- 3065-3072
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W1983431609
- Cited by
- 383
- References
- 39
- FWCI
- 3.95
- Type
- journal article
- Language
- en
- Open access
- closed
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