Cytomegalovirus-Infected Primary Endothelial Cells Trigger NKG2C+ Natural Killer Cells.
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.
Etablissement Franx00E7;ais du Sang, ImmunoVirologie et Polymorphisme Gx00E9;nx00E9;tique, Universitx00E9; de Nantes, Nantes, France.
Zakia
Z
Djaoud
Raphaëlle
R
Riou
Pierre-Jean
PJ
Gavlovsky
Souad
S
Mehlal
Céline
C
Bressollette
Nathalie
N
Gérard
Katia
K
Gagne
Béatrice
B
Charreau
Christelle
C
Retière
D001011:Aorta / Q000473:pathology; D015550:Cell Degranulation; D049109:Cell Proliferation; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology; D004730:Endothelium, Vascular / Q000276:immunology* / Q000821:virology; D005347:Fibroblasts / Q000276:immunology* / Q000821:virology; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007156:Immunologic Memory; D007694:Killer Cells, Natural / Q000276:immunology* / Q000821:virology; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets / Q000276:immunology* / Q000821:virology; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000378:metabolism; D054342:Receptors, KIR2DL1 / Q000378:metabolism; D000097625:HLA-E Antigens
D015395:Histocompatibility Antigens Class I; D055654:NK Cell Lectin-Like Receptor Subfamily C; D054342:Receptors, KIR2DL1; D000097625:HLA-E Antigens; C093100:KIR2DL1 protein, human; C527059:KLRC2 protein, human