Natural Killer Cell Receptor Repertoire and Their Ligands, and the Risk of CMV Infection After Kidney Transplantation

Hadaya, Karine; Rham, Casimir de; Bandelier, Cédric; Ferrari‐Lacraz, Sylvie; Jendly, S; Berney, Thierry; Bühler, Léo H.; Kaiser, Laurent; Seebach, Jörg Dieter; Jm, Tiercy; Martin, Pierre‐Yves; Villard, J.

doi:10.1111/j.1600-6143.2008.02431.x

Cited by 72 publications

(73 citation statements)

References 59 publications

(100 reference statements)

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“…The current literature on CMV infection and NK cell function is tilted overwhelmingly towards studies of solid organ and haematopoietic cell transplantation where patients are severely immunocompromised or elderly [23,32,39,40]. In CMV infection enhances NK cell activity 1 NK cells.…”

Section: Discussionmentioning

confidence: 99%

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Latent cytomegalovirus infection enhances anti-tumour cytotoxicity through accumulation of NKG2C+ NK cells in healthy humans

Bigley

Rezvani

Shah

et al. 2016

Clinical and Experimental Immunology

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SummaryCytomegalovirus (CMV) infection markedly expands NKG2C1/NKG2A2 NK cells, which are potent killers of infected cells expressing human leucocyte antigen (HLA)-E. As HLA-E is also over-expressed in several haematological malignancies and CMV has been linked to a reduced risk of leukaemic relapse, we determined the impact of latent CMV infection on NK cell cytotoxicity against four tumour target cell lines with varying levels of HLA-E expression. NK cell cytotoxicity against K562 (leukaemia origin) and U266 (multiple myeloma origin) target cells was strikingly greater in healthy CMV-seropositive donors than seronegative donors and was associated strongly with target cell HLA-E and NK cell NKG2C expression. NK cell cytotoxicity against HLA-E transfected lymphoma target cells (221.AEH) was $threefold higher with CMV, while NK cell cytotoxicity against non-transfected 721.221 cells was identical between the CMV groups. NK cell degranulation (CD107a

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Section: Discussionmentioning

confidence: 99%

“…1 NK cells help protect against CMV, as an increased proportion of these cells is associated with a lower risk of acute CMV infection in patients undergoing solid organ transplantation [23], and NKG2C…”

Section: Introductionmentioning

confidence: 99%

Latent cytomegalovirus infection enhances anti-tumour cytotoxicity through accumulation of NKG2C+ NK cells in healthy humans

Bigley

Rezvani

Shah

et al. 2016

Clinical and Experimental Immunology

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“…This effect is likely limited in vivo in most cases by the dilution of PLT-Ecto; however, at the time of allogeneic stem cell transplantation, PLT are often transfused in large amounts precisely at the time when the transplanted patients primarily need NK cell activity to prevent posttransplant viral infections and to exert an antitumoral effect (47)(48)(49). The decrease of the number of PLT-Ecto during transfusion can be achieved by transfusing very fresh PLT (the release of Ecto increases with storage time).…”

Section: Discussionmentioning

confidence: 99%

Platelet-Derived Ectosomes Reduce NK Cell Function

Sadallah

Schmied

Eken

et al. 2016

The Journal of Immunology

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Platelet (PLT) transfusions are potentially life saving for individuals with low PLT numbers; however, previous work revealed that PLT transfusions are associated with increased infection risk. During storage, PLT intended for transfusion continuously shed ectosomes (Ecto) from their surface, which express immunomodulatory molecules like phosphatidylserine or TGF-β1. Recently, PLT-Ecto were shown to reduce proinflammatory cytokine release by macrophages and to favor the differentiation of naive T cells toward regulatory T cells. Whether PLT-Ecto modify NK cells remains unclear. We exposed purified NK cells and full PBMCs from healthy donors to PLT-Ecto. We found a reduced expression of several activating surface receptors (NKG2D, NKp30, and DNAM-1) and decreased NK cell function, as measured by CD107a expression and IFN-γ production. Pretreatment of PLT-Ecto with anti–TGF-β1 neutralizing Ab restored surface receptor expression and NK cell function. We further observed a TGF-β1–mediated upregulation of miR-183, which, in turn, reduced DAP12, an important protein for stabilization and downstream signaling of several activating NK cell receptors. Again, these effects could antagonized, in part, when PLT-Ecto were preincubated with anti–TGF-β1 Ab. Erythrocyte Ecto did not affect NK cells. Polymorphonuclear cell Ecto expressed MHC class I and inhibited NK cell function. In addition, they induced the secretion of TGF-β1 by NK cells, which participated in an auto/paracrine manner in the suppressive activity of polymorphonuclear cell–derived Ecto. In sum, our study showed that PLT-Ecto could inhibit NK cell effector function in a TGF-β1–dependent manner, suggesting that recipients of PLT transfusions may experience reduced NK cell function.

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“…7). Several studies have reported an association between the KIR and HLA genotype and the development of CMV infection following hematopoietic stem cell (37) and solid-organ (38,39) transplantation. Moreover, a recent study (22) showed increased susceptibility to developing symptomatic primary CMV infection in immunocompetent adults carrying an AA haplotype or the HLA-Bw4 T allele.…”

Section: Discussionmentioning

confidence: 99%

Severe Symptomatic Primary Human Cytomegalovirus Infection despite Effective Innate and Adaptive Immune Responses

Riou

Bressollette-Bodin

Boutoille³

et al. 2017

J Virol

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Primary human cytomegalovirus (HCMV) infection usually goes unnoticed, causing mild or no symptoms in immunocompetent individuals. However, some rare severe clinical cases have been reported without investigation of host immune responses or viral virulence. In the present study, we investigate for the first time phenotypic and functional features, together with gene expression profiles in immunocompetent adults experiencing a severe primary HCMV infection. Twenty primary HCMV-infected patients (PHIP) were enrolled, as well as 26 HCMVseronegative and 39 HCMV-seropositive healthy controls. PHIP had extensive lymphocytosis marked by massive expansion of natural killer (NK) and T cell compartments. Interestingly, PHIP mounted efficient innate and adaptive immune responses with a deep HCMV imprint, revealed mainly by the expansion of NKG2C ϩ NK cells, CD16 ϩ V␦2(Ϫ) ␥␦ T cells, and conventional HCMV-specific CD8 ϩ T cells. The main effector lymphocytes were activated and displayed an early immune phenotype that developed toward a more mature differentiated status. We suggest that both massive lymphocytosis and excessive lymphocyte activation could contribute to massive cytokine production, known to mediate tissue damage observed in PHIP. Taken together, these findings bring new insights into the comprehensive understanding of immune mechanisms involved during primary HCMV infection in immunocompetent individuals.IMPORTANCE HCMV-specific immune responses have been extensively documented in immunocompromised patients and during in utero acquisition. While it usually goes unnoticed, some rare severe clinical cases of primary HCMV infection have been reported in immunocompetent patients. However, host immune responses or HCMV virulence in these patients has not so far been investigated. In the present study, we show massive expansion of NK and T cell compartments during the symptomatic stage of acute HCMV infection. The patients mounted efficient innate and adaptive immune responses with a deep HCMV imprint. The massive lymphocytosis could be the result of nonadapted or uncontrolled immune responses limiting the effectiveness of the specific responses mounted. Both massive lymphocytosis and excessive lymphocyte activation could contribute to massive cytokine production, known to mediate tissue damage. Furthermore, we cannot exclude a delayed immune response caused by immune escape established by HCMV strains.

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Natural Killer Cell Receptor Repertoire and Their Ligands, and the Risk of CMV Infection After Kidney Transplantation

Cited by 72 publications

References 59 publications

Latent cytomegalovirus infection enhances anti-tumour cytotoxicity through accumulation of NKG2C+ NK cells in healthy humans

Latent cytomegalovirus infection enhances anti-tumour cytotoxicity through accumulation of NKG2C+ NK cells in healthy humans

Platelet-Derived Ectosomes Reduce NK Cell Function

Severe Symptomatic Primary Human Cytomegalovirus Infection despite Effective Innate and Adaptive Immune Responses

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