Regulation of immune cell function and differentiation by the NKG2D receptor

Zafirova, Biljana; Wensveen, Felix M.; Gulin, Maja; Polić, Bojan

doi:10.1007/s00018-011-0797-0

Cited by 156 publications

(88 citation statements)

References 139 publications

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“…Hcst 2/2 mice (13) were obtained from Dr. M Colonna. Klrk1 2/2 and Klrk1 D/D mice were generated as described previously (7,14). In brief, in Klrk1 2/2 mice both transcriptional start codons of the Klrk1 gene have been deleted and exon 3 is replaced by an enhanced GFP cassette.…”

Section: Micementioning

confidence: 99%

NKG2D Induces Mcl-1 Expression and Mediates Survival of CD8 Memory T Cell Precursors via Phosphatidylinositol 3-Kinase

Wensveen

Lenartić

Jelenčić

et al. 2013

The Journal of Immunology

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Memory formation of activated CD8 T cells is the result of a specific combination of signals that promote long-term survival and inhibit differentiation into effector cells. Much is known about initial cues that drive memory formation, but it is poorly understood which signals are essential during the intermediate stages before terminal differentiation. NKG2D is an activating coreceptor on Ag-experienced CD8 T cells that promotes effector cell functions. Its role in memory formation is currently unknown. In this study, we show that NKG2D controls formation of CD8 memory T cells by promoting survival of precursor cells. We demonstrate that NKG2D enhances IL-15–mediated PI3K signaling of activated CD8 T cells, in a specific phase of memory cell commitment, after activation but before terminal differentiation. This signal is essential for the induction of prosurvival protein Mcl-1 and precursor cell survival. In vivo, NKG2D deficiency results in reduced memory cell formation and impaired protection against reinfection. Our findings show a new role for PI3K and the NKG2D/IL-15 axis in an underappreciated stage of effector to memory cell transition that is essential for the generation of antiviral immunity. Moreover, we provide novel insights how these receptors control both effector and memory T cell differentiation.

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Section: Micementioning

confidence: 99%

NKG2D Induces Mcl-1 Expression and Mediates Survival of CD8 Memory T Cell Precursors via Phosphatidylinositol 3-Kinase

Wensveen

Lenartić

Jelenčić

et al. 2013

The Journal of Immunology

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“…NKG2D ligands are expressed on the surface of tumor cells. NKG2D has been revealed to trigger natural immune cell-mediated cytotoxicity against a variety of tumor cells (22,23), but NKG2D-mediated cytotoxicity requires NKG2D ligands expressed on target cells and the expression of NKG2D receptors on the surface of immune cells (11).…”

Section: Discussionmentioning

confidence: 99%

Role of NKG2D in cytokine-induced killer cells against lung cancer

Zhang

et al. 2017

Oncology Letters

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Abstract.It has been previously demonstrated that cytokine-induced killer (CIK) cells possess potent cytotoxicity against various cancer cells, including lung cancer cells. However, the mechanism by which CIK cells recognize lung cancer cells has not been understood. The interaction between killer cell lectin like receptor K1 (NKG2D) receptor and NKG2D ligands was demonstrated to serve an important role in target cell killing by natural killer cells. The present study investigated whether NKG2D receptor and NKG2D ligand interactions are involved in the CIK-directed killing of lung cancer cells. The expression of MICA and ULBP2 was detected in tumor and healthy tissue samples. The expression of MICA and ULBP2 in tumor tissue samples was higher compared with that in the healthy control tissue. The expression of NKG2D ligands was analyzed in A549 and Q56 cells through reverse transcription-quantitative polymerase chain reaction and flow cytometry. The results demonstrated that the lung cancer cell lines markedly expressed the NKG2D ligands. Furthermore, NKG2D ligand-expressing lung cancer cells were targeted by CIK cells, which was partially blocked by treating CIK cells with an antibody against NKG2D. The data of the current study has demonstrated that the NKG2D-NKG2D ligand interaction serves an essential role in mediating lung cancer cell killing by CIK cells.

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“…NKG2D recognizes a number of MHC-class-I-related molecules, major histocompatibility complex class I chain-related molecule (MIC) A/B and UL16-binding protein (ULBP) expressed on cells in stressful conditions, such as transformation [22]. Owing to their ability to trigger activation of the immune system, it has now been shown that their expression is very tightly controlled at transcriptional level [23]. NKG2D is a pivotal activating receptor that upon binding stress-induced ligands and phosphorylation of intracellular adaptor protein DNAX-activation protein 10 (DAP10) recruits various signaling pathways and induces tumor cytotoxicity [24].…”

Section: Natural Killer Group 2dmentioning

confidence: 99%

The Role of Activating and Inhibitory NK Cell Receptors in Antitumor Immune Response

Konjević¹,

Vuletić²,

Martinović³

et al. 2017

Natural Killer Cells

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Natural killer (NK) cells express many newly identiied activating and inhibitory receptors that upon engagement by cognate ligands on target tumor cells regulate NK cell antitumor activity. Recently, several paired NK cell receptor families that include receptors with similar binding speciicities but opposite function have been deined. The expression of most important activating receptors, natural killer group 2D (NKG2D), natural cytotoxic receptors (NCR), DNAX accessory molecule-1 (DNAM1) and activating killer cell immunoglobulin-like receptors (KAR) is often decreased, while the expression of most prominent inhibitory NK cell receptors, killer cell inhibitory immunoglobulin-like receptors (KIR) and CD94/NKG2A, may occasionally be increased in malignancies. These data indicate that impaired NK cell antitumor response results from NK cell receptor alterations induced by suppressive factors in the tumor microenvironment, including cytokines, growth factors, enzymes and metabolites, as well as by chronic NK cell receptor engagement by the tumor. The established alterations in NK cell receptor expression in cancer patients represent potential disease biomarkers and may aid in choosing therapies that upregulate activating or block inhibitory receptor function. Accumulating knowledge of NK cell biology has been helpful in creating novel therapeutic approaches that by release from tumor-inluenced immunosuppression potentiate NK cell activity in cancer patients.

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Regulation of immune cell function and differentiation by the NKG2D receptor

Cited by 156 publications

References 139 publications

NKG2D Induces Mcl-1 Expression and Mediates Survival of CD8 Memory T Cell Precursors via Phosphatidylinositol 3-Kinase

NKG2D Induces Mcl-1 Expression and Mediates Survival of CD8 Memory T Cell Precursors via Phosphatidylinositol 3-Kinase

Role of NKG2D in cytokine-induced killer cells against lung cancer

The Role of Activating and Inhibitory NK Cell Receptors in Antitumor Immune Response

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