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Cited by 383

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

Verneris, Michael R., Karami, Mobin, Baker, Jeanette, Jayaswal, Anishka, Negrin, Robert S.·2004·Blood

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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Crossref · 10.1182/blood-2003-06-2125

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Metadata

Authors
Verneris, M. R., Karami, M., Baker, J., Jayaswal, A., & Negrin, R. S.
Venue
Blood
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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CoChat. (2026). Citation check: Role of NKG2D signaling in the cytotoxicity of activated and expanded CD8+ T cells. https://app.cochat.ai/papers/10.1182/blood-2003-06-2125
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Verneris, M. R., Karami, M., Baker, J., Jayaswal, A., & Negrin, R. S. (2004). Role of NKG2D signaling in the cytotoxicity of activated and expanded CD8+ T cells. Blood. https://doi.org/10.1182/blood-2003-06-2125

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