Divergent effects of FcγRIIIA ligands on the functional activities of human natural killer cells <i>in vitro</i>

Sulica, Andrei; Metes, Diana; Gherman, M; Whiteside, Theresa L.; Herberman, Ronald B.

doi:10.1002/eji.1830260602

Cited by 26 publications

(28 citation statements)

References 21 publications

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“…The recruitment of CD69 to the surface of NK cells, triggers cytotoxic activity and cytokine production (40). The cross-linking of CD16 molecules on the NK cell surface, triggers Ab-dependent cellular cytotoxicity (ADCC) and cytokine production (64). The recruitment of IL-2R on NK cells, triggers IFN-␥ production, cytotoxic activity, and cell proliferation (31,32).…”

Section: Discussionmentioning

confidence: 99%

Specific Signaling Pathways Triggered by IL-2 in Human Vγ9Vδ2 T Cells: An Amalgamation of NK and αβ T Cell Signaling

Lafont

Loisel-Meyer

Dudal

et al. 2003

The Journal of Immunology

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The global immune response can be simplified into two components: the innate and the acquired systems. The innate immune response comprises primarily macrophages and NK cells, while B and T cells orchestrate the acquired response. Human Vγ9Vδ2 T cells represent a minor T cell subpopulation in blood (1–5%) that is activated via the TCR by small nonpeptidic molecules. Their percentage dramatically increases during the early phase of infection by intracellular pathogens, and they display many characteristics of NK cells, which places them at a unique position within the immune system. Our aim was to explore the behavior of these cells when they are activated by a receptor that is common to NK and αβ T cells, and to determine signaling pathways and biological responses induced in these cells through this receptor. Thus, we investigated whether Vγ9Vδ2 T cells behave as NK cells or as αβ T cells. We demonstrated that IL-2 activates not only STAT3, STAT5, the phosphatidylinositol 3-kinase pathway, and extracellular signal-regulated kinase-2 pathway, but also STAT4 as in NK cells, and the p38 mitogen-activated protein kinase pathway as in αβ T cells. Moreover, IL-2 induces the production of IFN-γ in Vγ9Vδ2 T cells as observed in NK cells. Due to their double profiles, Vγ9Vδ2 T cells are at the interface of the innate and the acquired immune response and may therefore not only modulate the activity of innate cells, but also influence Th1/Th2 differentiation.

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Section: Discussionmentioning

confidence: 99%

Specific Signaling Pathways Triggered by IL-2 in Human Vγ9Vδ2 T Cells: An Amalgamation of NK and αβ T Cell Signaling

Lafont

Loisel-Meyer

Dudal

et al. 2003

The Journal of Immunology

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“…Effector cells were treated with mIgG (1 mg/10 6 cells/ml) and incubated for 2 h at 37 C as previously described [21,22]. NK cells cultured in CCM medium alone were used as control.…”

Section: Methodsmentioning

confidence: 99%

Interaction of Human Immunoglobulin G with CD16 on Natural Killer Cells: Ligand Clearance, FcγRIIIA Turnover and Effects of Metalloproteinases on FcγRIIIA‐Mediated Binding, Signal Transduction and Killing‡

Moţa¹,

Moldovan²,

Călugăru³

et al. 2004

Scand J Immunol

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Human natural killer (NK) cells express low-affinity Fc immunoglobulin G (IgG) receptor (FcgRIIIA/CD16). The binding of monomeric IgG (mIgG) and F(ab 0 ) 2 fragments of 3G8 anti-CD16 monoclonal antibody (mAb) to FcgRIIIA was investigated by flow cytometry. Over 90% of NK cells bound endogenous IgG, and during incubation at 37 C, the FcgRIIIA occupancy decreased slowly. Approximately 90% of NK cells bind mIgG or F(ab 0 ) 2 fragments of 3G8 anti-CD16 mAb. The calculated half-time (T 1/2 ) of in vitro mIgG dissociation from FcgRIIIA was 130 min. By cross-linking the mIgG ligand with F(ab 0 ) 2 fragments of anti-human IgG antibody, the T 1/2 decreases to 85 min. In kinetics study, it has been shown that 125 I-mIgG bound to FcgRIIIA is slowly released in the culture supernatant, maybe eluted at acid pH, or partially internalized and degraded. The binding of IgG to FcgRIIIA was increased by 53.8% on cells cultured in the presence of RU36156, a matrix metalloproteinase (MMP) inhibitor. Furthermore, an increase in phosphorylation of Lyn tyrosine kinase, after cross-linking of mIgG-FcgRIIIA complex, was observed on NK cells treated with RU36156. When the FcgRIIIA was occupied by mIgG, the capacity of NK cells to kill K562 target cells was decreased by RU36156, because the MMP inhibitor protects CD16 from proteolysis. Our data demonstrate that binding of mIgG to human NK cells is followed by ligand dissociation and/or internalization, enzymatic degradation and exocytosis. The RU36156 MMP inhibitor protects FcgRIIIA from cleavage, augments NK-cell activation and may interfere in their killing capacity.

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“…Similarly, ligation of CD16 by mIgG can lead to reversible functional defects in NK cell activity that are related both to direct cell killing and ADCC and to production of CC chemokines and cytokines, including IFN-␥ (61,62). However, in conjunction with other factors, such as costimulation signals, ligation of CD16 by mIgG can upregulate NK cell proliferation and cytokine release (61,62). NK cell defects induced by mIgG binding to CD16 were reversed in the presence of added IFN-␥ or interleukin-2 or if the incubation time of NK cells with mIgG was increased.…”

Section: Cd3mentioning

confidence: 99%

“…Ligation of CD16 by monoclonal antibodies (MAbs) to CD16 or IgG immune complexes (IgGICs) and recognition of Fc fragments bound to cell surface antigens can lead to activation, cytokine secretion, cytotoxicity, and/or proliferation of NK cells (67); however, CD16 ligation on cytokine-activated NK cells results in apoptosis (56). CD16 preferentially recognizes IgG bound to antigen, but CD16 recognition and binding of soluble monomeric IgG (mIgG) can occur in vivo, is labile, and can inhibit NK cell activity (23,61,62). Although circulating ICs containing HIV have been detected in serum and plasma samples from infected persons (52,54), the exact impact of ICs on the various subsets of NK cells has not been defined.…”

mentioning

confidence: 99%

Simian Immunodeficiency Virus (SIV)/Immunoglobulin G Immune Complexes in SIV-Infected Macaques Block Detection of CD16 but Not Cytolytic Activity of Natural Killer Cells

Wei

Stallworth

Vance

et al. 2006

Clin Vaccine Immunol

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Natural killer cells are components of the innate immune system that play an important role in eliminating viruses and malignant cells. Using simian immunodeficiency virus (SIV) infection of macaques as a model, flow cytometry revealed a gradual loss of CD16؉ NK cell numbers that was associated with disease progression. Of note, the apparent loss of NK cells was detected in whole-blood samples but not in isolated peripheral blood mononuclear cells (PBMC), suggesting that an inhibitor(s) of the antibody used to detect CD16, the low-affinity immunoglobulin G (IgG) receptor, was present in blood but was removed during PBMC isolation. (Actual decreases in CD16؉ cell numbers in PBMC generally were not detected until animals became lymphopenic.) The putative decrease in CD16 ؉ cell numbers in whole blood correlated with increasing SIV-specific antibody titers and levels of plasma virion RNA. With the addition of increasing amounts of plasma from progressor, but not nonprogressor, macaques to PBMC from an uninfected animal, the apparent percentage of CD16

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Divergent effects of FcγRIIIA ligands on the functional activities of human natural killer cells in vitro

Cited by 26 publications

References 21 publications

Specific Signaling Pathways Triggered by IL-2 in Human Vγ9Vδ2 T Cells: An Amalgamation of NK and αβ T Cell Signaling

Specific Signaling Pathways Triggered by IL-2 in Human Vγ9Vδ2 T Cells: An Amalgamation of NK and αβ T Cell Signaling

Interaction of Human Immunoglobulin G with CD16 on Natural Killer Cells: Ligand Clearance, FcγRIIIA Turnover and Effects of Metalloproteinases on FcγRIIIA‐Mediated Binding, Signal Transduction and Killing‡

Simian Immunodeficiency Virus (SIV)/Immunoglobulin G Immune Complexes in SIV-Infected Macaques Block Detection of CD16 but Not Cytolytic Activity of Natural Killer Cells

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