Cytomegalovirus-Infected Primary Endothelial Cells Trigger NKG2C⁺ Natural Killer Cells

Abstract

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.

NK-cells that identify glycopatterns and their anti-tumor potential against a background of epidemically significant viral infections

“…Adaptive RL expression and distribution of RL types between cells populations is influenced by an overall state of a body (heredity, age, sex, immune system state, other factors), pathologies, types of viruses and tumors [8, 10,35].…”

“…Limited immunologic functions performed by MHC-E/NKG2 system develop in a human body when functions of MHC-I/KIR system expand [39]. Expression of HLA-class-I drops drastically with KIR participation in cells infected with viruses, while expression of HLA-E (is usually detected on tumor cells; is a section where RL are bound) is more stable and is supported by activating NKG2-receptors [10,12,27,39].…”

“…*NKG2A+ against EBV [11]. *NKG2А+KIR+, NKG2A+NKG2C-KIR-, NKG2С+KIR+; CMV-infected derivatives of human monocytes; KIR+NKG2C+ doesn't influence a response by KIR-NKG2C-*NKG2C+; U266 (cells of human multiple myeloma) from CMV-seropositive donors, K562 (leukemic human cells); expansion of the population in a body is stimulated [6,10], occurrence of latent CMV in healthy donors becomes apparent via stronger NKcytotoxicity [6]. *NKG2C+CD57+; lymphomas; the population expands as a response to CMV [31].…”

“…* NKG2C+; anti-tumor application of ligands for NKG2С [33]. * NKG2C+; CMV-infected endothelial cells of the aorta; character of population modulation depends on a type of CMV-infected cells [10]. *NKG2C+NKG2A-; 221.AEH (transfected HLA-E+-cells of human lymphoma); NK-cytotoxicity is three times higher than in non-transfected ones, 221.AEH и ИЛ15 make for expansion of the population in a body [6,33].…”

NK-cells that identify glycopatterns and their anti-tumor potential against a background of epidemically significant viral infections

“…На адаптивную экспрессию РЛ и распределение типов РЛ между популяциями клеток оказывают влияние общий статус организма (наследственность, возраст, пол, состояние иммунной системы, другое), наличие патологий, типы вирусов и опухолей [8,10,35].…”