Effects of Cytomegalovirus Infection on Growth Factor Production in Endothelial Cells and Fibroblasts

Js, Garrett; Jc, Narus; Jf, Bohnsack; De, Carling; Kg, Grieves; Wj, Waldman; Re, Shaddy

doi:10.1203/00006450-199512000-00029

Cited by 7 publications

(5 citation statements)

References 25 publications

(26 reference statements)

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“…Stock suspensions of CMV strain VHL/E (provided by Prof. James Waldman, Columbus, Ohio, USA) were produced as previously described [18,24]. CMV VHL/E was first inoculated onto confluent and low-passaged human umbilical vein EC (HUVEC; PromoCell, Heidelberg, Germany) monolayers in 25-cm 2 gelatin-coated culture flasks.…”

Section: Methodsmentioning

confidence: 99%

Cytomegalovirus-Infected Primary Endothelial Cells Trigger NKG2C<sup>+</sup> Natural Killer Cells

et al. 2016

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Among innate cells, natural killer (NK) cells play a crucial role in the defense against cytomegalovirus (CMV). In some individuals, CMV infection induces the expansion of NKG2C⁺ NK cells that persist after control of the infection. We have previously shown that KIR2DL⁺ NK cells, in contrast to NKG2C⁺ NK cells, contribute to controlling CMV infection using a CMV-infected monocyte-derived dendritic cell (MDDC) model. However, the nature of CMV-infected cells contributing to the expansion of the NKG2C⁺ NK cell subset remains unclear. To gain more insight into this question, we investigated the contribution of NKG2C⁺ NK cell activation by CMV-infected primary human aortic endothelial cells (EC) isolated from kidney transplant donors, which constitutively express the human leukocyte antigen (HLA)-E molecule. Here, we show that, although classic HLA class I expression was drastically downregulated, nonclassic HLA-E expression was maintained in CMV-infected EC. By comparing HLA expression patterns in CMV-infected EC, fibroblasts and MDDC, we demonstrate a cell-dependent modulation of HLA-E expression by CMV infection. NKG2C⁺ NK cell degranulation was significantly triggered by CMV-infected EC regardless of the nature of the HLA-E allele product. EC, predominantly present in vessels, may constitute a privileged site for CMV infection that drives a ‘memory' NKG2C⁺ NK cell subset.

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Section: Methodsmentioning

confidence: 99%

Cytomegalovirus-Infected Primary Endothelial Cells Trigger NKG2C<sup>+</sup> Natural Killer Cells

et al. 2016

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“…Stock suspensions of CMV strain VHL/E (provided by the Prof. James Waldman, Columbus, OH) were produced as previously described (26). Of note, the full genomic sequence of VHL/E is not available and thus its genetic content has not been established.…”

Section: Preparation and Infection Of Idcsmentioning

confidence: 99%

Amplified NKG2C+ NK Cells in Cytomegalovirus (CMV) Infection Preferentially Express Killer Cell Ig-like Receptor 2DL: Functional Impact in Controlling CMV-Infected Dendritic Cells

Djaoud

David

Bressollette

et al. 2013

The Journal of Immunology

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CMV infection represents a major complication in hematopoietic stem cell transplantation, which compromises graft outcome. Downregulation of HLA class I expression is one mechanism by which CMV evades T cell–mediated immune detection, rendering infected cells vulnerable to killer cell Ig-like receptor (KIR)+ NK cells. In this study, we observed that the amplified NKG2C+ NK cell population observed specifically in CMV seropositive individuals mainly expressed KIR2DL receptors. We have shown that HLA class I expression was downregulated on CMV-infected immature dendritic cells (iDCs), which escape to HLA-A2-pp65–specific T lymphocytes but strongly trigger the degranulation of KIR2D+ NK cells. CMV infection conferred a vulnerability of C2C2+ iDCs to educated KIR2DL1+ and KIR2DL3+ NK cell subsets. Alloreactivity of KIR2DL1+ NK cell subsets against C1C1+ iDCs was maintained independently of CMV infection. Unexpectedly, CMV-infected C1C1+ iDCs did not activate KIR2DL3+ NK cell reactivity, suggesting a potential CMV evasion to KIR2DL3 NK cell recognition. Altogether, the coexpression of KIR and NKG2C on expanded NK cell subsets could be related to a functional contribution of KIR in CMV infection and should be investigated in hematopoietic stem cell transplantation, in which the beneficial impact of CMV infection has been reported on the graft-versus-leukemia effect.

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“…therefore, indicates losses of EC during the whole three-step quantification procedure. Because functional and morphological properties of CMVinfected EC are seriously disturbed (1,2,5,9,21,22,25,26,28), isolation characteristics of CEC from patients could differ from noninfected EC. In particular, expression of surface antigens is influenced by infection of EC with CMV (2,9,21,25).…”

Section: Discussionmentioning

confidence: 99%

A Sensitive Method for Quantifying Cytomegalic Endothelial Cells in Peripheral Blood from Cytomegalovirus-Infected Patients

Kas-Deelen¹,

Harmsen²,

Maar³

et al. 1998

Clin Diagn Lab Immunol

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A sensitive method has been developed for the quantification of cytomegalic endothelial cells (CEC) in peripheral blood (PB) of patients with active cytomegalovirus (CMV) infections. The three subsequent key steps of this method are density centrifugation to enrich endothelial cells (EC) in the mononuclear cell (MNC) fraction, EC-specific staining, and fluorescence-activated cell sorting (FACS) of EC onto adhesion slides. The FACS method was compared with the conventional method of cytocentrifugation of the MNC fraction onto slides, followed by EC-specific staining. The main advantage of the additional steps for the isolation and quantification of CEC in PB by FACS is a 10-times-greater sensitivity than by cytocentrifugation of the MNC fraction alone. The recovery percentages of EC from whole blood were comparable for both methods. Recoveries of EC obtained after FACS were 53% ± 16.5%, (mean ± standard deviation), and recoveries of EC obtained after cytocentrifugation of the MNC fraction were 43% ± 4.3%. In patients with active CMV infection, 5 to 72 CEC were detected by FACS, equivalent to 0.8 to 9.0 CEC/ml of blood. With this method for isolation and quantification, the characterization of CEC in PB of patients with CMV-associated clinical symptoms, as well as the quantification of EC in PB of patients with pathophysiological manifestations involving endothelial damage that are different from those caused by CMV infections, can be performed.

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Effects of Cytomegalovirus Infection on Growth Factor Production in Endothelial Cells and Fibroblasts

Cited by 7 publications

References 25 publications

Cytomegalovirus-Infected Primary Endothelial Cells Trigger NKG2C<sup>+</sup> Natural Killer Cells

Cytomegalovirus-Infected Primary Endothelial Cells Trigger NKG2C<sup>+</sup> Natural Killer Cells

Amplified NKG2C+ NK Cells in Cytomegalovirus (CMV) Infection Preferentially Express Killer Cell Ig-like Receptor 2DL: Functional Impact in Controlling CMV-Infected Dendritic Cells

A Sensitive Method for Quantifying Cytomegalic Endothelial Cells in Peripheral Blood from Cytomegalovirus-Infected Patients

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