DNAM-1, A Novel Adhesion Molecule Involved in the Cytolytic Function of T Lymphocytes

Shibuya, Akira; Campbell, David G.; Hannum, Charles; Yssel, Hans; Franz-Bacon, Karin; McClanahan, Terrill K.; Kitamura, Toshio; Nicholl, Jillian; Sutherland, Grant R.; Lanier, Lewis L.; Phillips, Joseph H.

doi:10.1016/s1074-7613(00)70060-4

Cited by 542 publications

(482 citation statements)

References 40 publications

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“…In that study, stimulation of CD8 1 T cells by anti-DNAM-1 in a redirected antibody-dependent cytotoxicity assay resulted in killing of target cells reaching similar levels as anti-CD3 stimulation. Here, we found that DNAM-1 was expressed by the CD4 1 CD28 À T-cell subset, but in contrast to the previous study on CD8 1 T cells [27], stimulation by anti-DNAM-1 alone did not induce IFN-g production nor degranulation of CD4 1 T cells. We further demonstrate that 2B4 is expressed by most CD4 1 CD28 À T cells in RA but less frequently on CD28 1 T cells.…”

Section: Discussioncontrasting

confidence: 99%

“…NKR have previously been described to be expressed on highly differentiated T cells, although their role remains elusive. DNAM-1 has been shown to be expressed on subsets of both CD4 1 and CD8 1 T cells [27]. In that study, stimulation of CD8 1 T cells by anti-DNAM-1 in a redirected antibody-dependent cytotoxicity assay resulted in killing of target cells reaching similar levels as anti-CD3 stimulation.…”

Section: Discussionmentioning

confidence: 87%

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Activating NK‐cell receptors co‐stimulate CD4⁺CD28⁻ T cells in patients with rheumatoid arthritis

et al. 2010

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Effector T‐cell responses can be modulated by competing positive or negative signals transduced by NK‐cell receptors (NKR). In the CD4+ T‐cell population, the expression of NKR is primarily found in the CD4+CD28− T‐cell subset, also known as CD28null T cells. These T cells are frequently found in rheumatoid arthritis (RA) and other inflammatory disorders, suggesting that signaling through NKR may play a role in the autoimmune reaction. Here we aimed to dissect the phenotype and function of NKR‐expressing CD4+CD28− T cells in patients with RA. By analyzing a broad array of NKR on CD4+CD28− T cells we found a significant expression of the co‐activating receptors 2B4 (CD244), DNAM‐1 (CD226), and CRACC. Pair‐wise ligations of 2B4 with DNAM‐1 and/or NKG2D lead to increased effector functions of primary CD4+CD28− T cells to suboptimal levels of anti‐CD3 stimulation. Using multi‐parameter flow cytometry, we demonstrate that such co‐ligation led to an increased magnitude in overall responsiveness without changing qualitative aspects of the response. Altogether these results demonstrate a pattern of additive effects in NKR‐mediated functional modulation of CD4+CD28− T cells in RA. This may have consequences for the inflammatory responses imposed by these cells, thus influencing disease manifestations.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 87%

Activating NK‐cell receptors co‐stimulate CD4⁺CD28⁻ T cells in patients with rheumatoid arthritis

et al. 2010

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“…Expression of DNAM-1 and CD96 were also found on ab T cells as previously described [23]. In parallel, we show that HCC cell lines expressed the ligands Nectin-2 and Necl-5 on their cell surface.…”

Section: Discussionsupporting

confidence: 86%

“…DNAM-1 is a 65 kDa transmembrane glycoprotein physically and functionally associated with lymphocyte functionassociated antigen-1 (LFA-1) [22]. DNAM-1 engagement by mAbmediated cross-linking triggers tyrosine phosphorylation and its recruitment into the membrane rafts [23,24]. Moreover, DNAM-1 functions such as adhesion are dependent on the phosphorylation of serine residue 329 in the cytoplasmic domain by the PKC [25].…”

Section: Discussionmentioning

confidence: 99%

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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“…24,25,31 Besides NCRs, other activating receptors, including NKG2D and DNAM-1, contribute to trigger the NK cell-mediated cytotoxicity. 32-34 Ligands specific for these receptors have been extensively characterized: MICA/B and ULBPs molecules are recognized by NKG2D, while PVR and Nectin-2 (belonging to the Nectin family), are ligands for DNAM-1. 32,33,35,36 …”

Section: Introductionmentioning

confidence: 99%

Nidogen-1 is a novel extracellular ligand for the NKp44 activating receptor

et al. 2018

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The release of soluble ligands of activating Natural Killer (NK) cell receptors may represent a regulatory mechanism of NK cell function both in physiologic and in pathologic conditions. Here, we identified the extracellular matrix protein Nidogen-1 (NID1) as a ligand of NKp44, an important activating receptor expressed by activated NK cells. When released as soluble molecule, NID1 regulates NK cell function by modulating NKp44-induced IFN-γ production or cytotoxicity. In particular, it also modulates IFN-γ production induced by Platelet-Derived Growth Factor (PDGF)-DD following NKp44 engagement. We also show that NID1 may be present at the cell surface. In this form or when bound to a solid support (bNID1), NID1 fails to induce NK cell cytotoxicity or cytokine release. However, analysis by mass spectrometry revealed that exposure to bNID1 can induce in human NK cells relevant changes in the proteomic profiles suggesting an effect on different biological processes.

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DNAM-1, A Novel Adhesion Molecule Involved in the Cytolytic Function of T Lymphocytes

Cited by 542 publications

References 40 publications

Activating NK‐cell receptors co‐stimulate CD4⁺CD28⁻ T cells in patients with rheumatoid arthritis

Activating NK‐cell receptors co‐stimulate CD4⁺CD28⁻ T cells in patients with rheumatoid arthritis

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

Nidogen-1 is a novel extracellular ligand for the NKp44 activating receptor

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DNAM-1, A Novel Adhesion Molecule Involved in the Cytolytic Function of T Lymphocytes

Cited by 542 publications

References 40 publications

Activating NK‐cell receptors co‐stimulate CD4+CD28− T cells in patients with rheumatoid arthritis

Activating NK‐cell receptors co‐stimulate CD4+CD28− T cells in patients with rheumatoid arthritis

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

Nidogen-1 is a novel extracellular ligand for the NKp44 activating receptor

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Product

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Activating NK‐cell receptors co‐stimulate CD4⁺CD28⁻ T cells in patients with rheumatoid arthritis

Activating NK‐cell receptors co‐stimulate CD4⁺CD28⁻ T cells in patients with rheumatoid arthritis