Elusive Role of the CD94/NKG2C NK Cell Receptor in the Response to Cytomegalovirus: Novel Experimental Observations in a Reporter Cell System

Pupuleku, Aldi; Costa‐García, Marcel; Farré, Domènec; Hengel, Hartmut; Angulo, Ana; Muntasell, Aura; López‐Botet, Miguel

doi:10.3389/fimmu.2017.01317

Cited by 20 publications

(16 citation statements)

References 54 publications

(58 reference statements)

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“…NK cell memory has been initially described in mice infected by MCMV, where Ly49H + NK cells quickly expand and have stronger responses after a secondary encounter with the virus (91). Interestingly, a similar NK cell subset has been identified in humans, where NK cells expressing NKG2C are expanded and persist in CMV infected patients (92). Both Ly49H and NKG2C bind viral determinants, highlighting how NK cell memory is linked with the ability of NK cells to directly recognize viruses (93,94).…”

Section: Nk Cell Effector Functions and Memorymentioning

confidence: 95%

Flattening the COVID-19 Curve With Natural Killer Cell Based Immunotherapies

et al. 2020

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Natural Killer (NK) cells are innate immune responders critical for viral clearance and immunomodulation. Despite their vital role in viral infection, the contribution of NK cells in fighting SARS-CoV-2 has not yet been directly investigated. Insights into pathophysiology and therapeutic opportunities can therefore be inferred from studies assessing NK cell phenotype and function during SARS, MERS, and COVID-19. These studies suggest a reduction in circulating NK cell numbers and/or an exhausted phenotype following infection and hint toward the dampening of NK cell responses by coronaviruses. Reduced circulating NK cell levels and exhaustion may be directly responsible for the progression and severity of COVID-19. Conversely, in light of data linking inflammation with coronavirus disease severity, it is necessary to examine NK cell potential in mediating immunopathology. A common feature of coronavirus infections is that significant morbidity and mortality is associated with lung injury and acute respiratory distress syndrome resulting from an exaggerated immune response, of which NK cells are an important component. In this review, we summarize the current understanding of how NK cells respond in both early and late coronavirus infections, and the implication for ongoing COVID-19 clinical trials. Using this immunological lens, we outline recommendations for therapeutic strategies against COVID-19 in clearing the virus while preventing the harm of immunopathological responses.

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Section: Nk Cell Effector Functions and Memorymentioning

confidence: 95%

Flattening the COVID-19 Curve With Natural Killer Cell Based Immunotherapies

et al. 2020

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“…51,52 However, attempts to demonstrate NKG2C-mediated activation of NK cell effector functions against CMV-infected cells were unsuccessful, and similar negative results have been obtained with a CD94/NKG2C+ reporter cell line. 53 Recently, HLA-E presentation of leader peptide sequences from the UL40 CMV protein was reported to activate NKG2C+ NK cells under certain experimental conditions. 54 Moreover, adaptive NKG2C+ NK cells proficiently mediate specific antibody-dependent effector functions, particularly TNF-α and IFN-γ production, triggered through CD16 in a CD2-dependent manner against different targets, including CMV-infected cells.…”

Section: Nkg2c+ Nk Cells Independently Predict Risk Of CMV Infectionmentioning

confidence: 99%

Pretransplant adaptive NKG2C+ NK cells protect against cytomegalovirus infection in kidney transplant recipients

Ataya

Redondo‐Pachón

Llinàs‐Mallol

et al. 2020

American Journal of Transplantation

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Cytomegalovirus (CMV) infection constitutes a complication for kidney transplant recipients (KTR) and CMV‐specific T cells reduce the risk of viral replication in seropositive patients. CMV promotes the adaptive differentiation and expansion of an NK cell subset, hallmarked by expression of the CD94/NKG2C receptor with additional characteristic features. We previously reported an association of pretransplant NKG2C+ NK cells with a reduced incidence of CMV infection. We have strengthened the analysis in cryopreserved peripheral blood mononuclear cells from an enlarged KTR cohort (n = 145) with homogeneous immunosuppression, excluding cases at low risk of infection (ie, CMV D−R−) or receiving antiviral prophylaxis. Moreover, adaptive NKG2C+ NK cell–associated markers (ie, NKG2A, CD57, Immunoglobulin‐like transcript 2 [LIR1 or LILRB1], FcεRI γ chain, and Prolymphocytic Leukemia Zinc Finger transcription factor) as well as T lymphocyte subsets were assessed by multicolor flow cytometry. The relation of NKG2C+ NK cells with T cells specific for CMV antigens was analyzed in pretransplant patients (n = 29) and healthy controls (n = 28). Multivariate Cox regression and Kaplan‐Meier analyses supported that NKG2C+ NK cells bearing adaptive markers were specifically associated with a reduced incidence of posttransplant symptomatic CMV infection; no correlation between NKG2C+ NK cells and CMV‐specific T cells was observed. These results support that adaptive NKG2C+ NK cells contribute to control CMV infection in KTR.

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“…*NKG2C+ (predominantly); mice lymphomas; action performed by the population and caused by CMV occurrence takes place after allogenic transplantation [30]. * 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].…”

Section: Variety Of Nk-populations Typed By Receptor Lectinsmentioning

confidence: 99%

“…* 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]. *NKG2C+CD94+; Burkitt lymphoma; the population participates in protection of cooperation together with gamma-delta-Tcells [11].…”

Section: Variety Of Nk-populations Typed By Receptor Lectinsmentioning

confidence: 99%

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

Lakhtin¹,

Lakhtin²,

Алешкин³

et al. 2019

Health Risk Analysis

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Risks related to tumors development against a background of viral infections as well as factors that determine such risks or reduce them have not been examined profoundly so far. Our research goal was to accomplish a scientific review of research on a potential possessed by populations of lectin NK-cells (natural killers) in a body; such populations can have variable sets of lectin and other functionally significant cell surface receptors against tumors in a situation when viruses, including epidemically significant ones, penetrate a body. It is shown that cofunctioning of various receptors and their ligands that redistribute cytokines (glycopattern-identifying lectin (basis) receptors, Ig-similar receptors, cytotoxic receptors, and other effector (adjusting) receptors) plays a significant role in intercellular communications and effects produced by NK-populations. NK-populations network is a promising resource for body protection and it should be taken into account when developing new anti-tumor and anti-viralpreventive and medical strategies. When certain NK-populations with protective functions are absent in a body, it can be considered a new multi-factor risk of viral and oncologic diseases in an individual or a contingent living in a specific region. The reviewed data can be applied to develop new anti-tumor and anti-viral medications and vaccines as well as medical strategies. Probiotic lectins are promising ligands of intercellular communications associated with immune surveillance. Read online __________________________  Lakhtin M.V.

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Elusive Role of the CD94/NKG2C NK Cell Receptor in the Response to Cytomegalovirus: Novel Experimental Observations in a Reporter Cell System

Cited by 20 publications

References 54 publications

Flattening the COVID-19 Curve With Natural Killer Cell Based Immunotherapies

Flattening the COVID-19 Curve With Natural Killer Cell Based Immunotherapies

Pretransplant adaptive NKG2C+ NK cells protect against cytomegalovirus infection in kidney transplant recipients

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

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