Activated γδ T cells express the natural cytotoxicity receptor natural killer p44 and show cytotoxic activity against myeloma cells

Lilienfeld-Toal, M von; Nattermann, Jacob; Feldmann, Georg; Sievers, Elisabeth; Frank, Susanne; Strehl, John; Schmidt‐Wolf, Ingo G.H.

doi:10.1111/j.1365-2249.2006.03078.x

Cited by 79 publications

(65 citation statements)

References 31 publications

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“…Regarding gd T-cell-mediated cytotoxicity, it is likely that the overall lytic function of these cells reflects the net sum of multiple receptor-ligand interactions as illustrated here with DNAM-1 and NKG2D. In this regard, a recent paper by von Lilienfeld-Toal et al shows that the natural cytotoxicity receptor NKp46 expressed by gd T cells plays a role in their cytotoxic activity against myeloma [9]. Further studies are required to address the involvement of other NK receptor-ligand pairs in the recognition of HCC and to determine whether their expression is predictive of gd T-cell therapy efficiency.…”

Section: Discussionmentioning

confidence: 90%

“…The capacity of gd T cells to recognize human tumor cells in a nonrestricted MHC manner is well documented [3,4,7,9]. However, the requirements for recognition of malignant cells are not completely understood.…”

Section: Discussionmentioning

confidence: 99%

“…Immunological approaches using innate antitumor effector cells are currently being evaluated in clinical trials [2]. Vg9Vd2 T cells represent the major population of human peripheral blood gd T cells and display an in vitro non-MHCrestricted lytic activity against a broad panel of tumors including colon, kidney, liver, esophageal, small-lung cancers and myeloma [3][4][5][6][7][8][9]. The presence of tumor-infiltrating Vd2 1 T cells in tumorbearing livers of patients may support their potential role in tumor immunosurveillance of HCC [10].…”

Section: Introductionmentioning

confidence: 99%

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DNAX accessory molecule‐1 (CD226) promotes human hepatocellular carcinoma cell lysis by Vγ9Vδ2 T cells

et al. 2009

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Human Vc9Vd2 T lymphocytes can be activated by nonpeptidic antigens such as the mevalonate pathway-derived isopentenyl pyrophosphate or synthetic phosphoantigen such as bromohydrin pyrophosphate. They display a strong cytotoxic activity against several tumor types, including hepatocellular carcinoma (HCC). Little is known about the mechanisms underlying Vc9Vd2 T-cell recognition of tumor cells, but there is strong evidence that activating NK receptors play a role in cd T-cell cytotoxicity. In this study, we showed that the two NK receptors DNAX accessory molecule-1 (DNAM-1) and CD96 were expressed by Vc9Vd2 T cells. The ligands Nectin-like-5 specific of both DNAM-1 and CD96, and also Nectin-2, an additional ligand of DNAM-1, were present on all HCC cell lines analyzed. Furthermore, we demonstrated by mAb-mediated masking experiments that cytotoxicity against HCC cells as well as IFN-c production in cd T cells were dependent on DNAM-1. Our experiments indicated that Nectin-like-5 but not Nectin-2 was involved in DNAM-1-dependent cd T-cell functions. We did not reveal a role for CD96 in the killing of HCC cells. Finally, we showed by combined mAb-mediated blockade that DNAM-1 and NKG2D could cooperate in the cell lysis of HCC.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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DNAX accessory molecule‐1 (CD226) promotes human hepatocellular carcinoma cell lysis by Vγ9Vδ2 T cells

et al. 2009

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“…Similarly, mice genetically deficient in IL-15 lacked NK cells, indicating an obligate role for IL-15 in the development and functional maturation of these cells (26). More recently, IL-15 has been implicated in the up-regulation of NK cell receptor expression and function, as demonstrated for NKG2D (27) and NKp44 (28).…”

Section: N Atural Killer Cells Are a Class Of Lymphocytes Involved Inmentioning

confidence: 97%

A Soluble Form of the MHC Class I-Specific CD160 Receptor Is Released from Human Activated NK Lymphocytes and Inhibits Cell-Mediated Cytotoxicity

Giustiniani

Marie‐Cardine

Bensussan

2007

The Journal of Immunology

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CD160 is a GPI-anchored lymphocyte surface receptor in which expression is mostly restricted to the highly cytotoxic CD56dimCD16+ peripheral blood NK subset. We previously reported that MHC class I (MHC-I) molecules bind to CD160 receptors on circulating NK lymphocytes and that this interaction triggers their cytotoxic activity and cytokine production. We also observed that CD160 surface expression on NK cells is down-modulated upon activation with PMA or IL-2. In this study, we further report that short-time incubation of NK lymphocytes with IL-15 converts the membrane-bound CD160 to a soluble form through a proteolytic cleavage involving a metalloprotease. Thus, CD160 is no longer detected at the cell surface, but can be immunoprecipitated from the NK cell culture medium. Interestingly, CD160 transcript remains highly expressed during the process of protein shedding. In addition, we demonstrate that CD160 mRNA synthesis can be induced in CD56bright separated lymphocytes following exposure to IL-15. By producing a Flag-tagged soluble CD160 protein, we establish that its binding to MHC-I molecules results in the inhibition of the cytotoxic CD8+ T lymphocyte activity and of the CD160-mediated NK cell cytotoxicity. Thus, we show that activated NK lymphocytes release a soluble form of CD160 that functionally impairs the MHC-I-specific cytotoxic CD8+ T lymphocyte responsiveness.

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“…Finally, NK cells also express NCR (NKp30, NKp44 and NKp46) that are critically involved in tumor cell recognition [11]. In a marginal way, under particular conditions of activation,  T cells also express NKp44 [12].…”

Section: Introductionmentioning

confidence: 99%

PGE2 inhibits natural killer and γδ T cell cytotoxicity triggered by NKR and TCR through a cAMP-mediated PKA type I-dependent signaling

Martinet¹,

Jean²,

Dietrich³

et al. 2010

Biochemical Pharmacology

112

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inhibits Natural Killer and γδ T cell cytotoxicity triggered by NKR and TCR through a cAMPmediated PKA type I-dependent signaling. Biochemical Pharmacology, Elsevier, 2010, 80 (6) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Activated γδ T cells express the natural cytotoxicity receptor natural killer p44 and show cytotoxic activity against myeloma cells

Abstract: NKp44. To our knowledge, this is the first description of the expression of NKp44 on polyclonal γ γ γ γδ δ δ δ T cells.

Cited by 79 publications

References 31 publications

DNAX accessory molecule‐1 (CD226) promotes human hepatocellular carcinoma cell lysis by Vγ9Vδ2 T cells

DNAX accessory molecule‐1 (CD226) promotes human hepatocellular carcinoma cell lysis by Vγ9Vδ2 T cells

A Soluble Form of the MHC Class I-Specific CD160 Receptor Is Released from Human Activated NK Lymphocytes and Inhibits Cell-Mediated Cytotoxicity

PGE2 inhibits natural killer and γδ T cell cytotoxicity triggered by NKR and TCR through a cAMP-mediated PKA type I-dependent signaling

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