scholarly journals Common cytological and cytogenetic features of Epstein-Barr virus (EBV)-positive natural killer (NK) cells and cell lines derived from patients with nasal T/NK-cell lymphomas, chronic active EBV infection and hydroa vacciniforme-like eruptions

2003 ◽  
Vol 121 (5) ◽  
pp. 805-814 ◽  
Author(s):  
Yu Zhang ◽  
Hiroshi Nagata ◽  
Tatsuro Ikeuchi ◽  
Hiroyuki Mukai ◽  
Michiko K. Oyoshi ◽  
...  
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Cell Lines ◽  
Epstein Barr Virus ◽  
Nk Cell ◽  
Barr Virus ◽  
Ebv Infection ◽  
Hydroa Vacciniforme ◽  
Epstein Barr

scholarly journals Hydroa Vacciniforme and Hydroa Vacciniforme-Like Lymphoproliferative Disorder: A Spectrum of Disease Phenotypes Associated with Ultraviolet Irradiation and Chronic Epstein–Barr Virus Infection

2020 ◽  
Vol 21 (23) ◽  
pp. 9314
Author(s):  
Chien-Chin Chen ◽  
Kung-Chao Chang ◽  
L Jeffrey Medeiros ◽  
Julia Yu-Yun Lee
Keyword(s):  
T Cell ◽  
Natural Killer ◽  
Ultraviolet Irradiation ◽  
Epstein Barr Virus ◽  
Nk Cell ◽  
Current Evidence ◽  
Barr Virus ◽  
Ebv Infection ◽  
Hydroa Vacciniforme ◽  
Epstein Barr

Hydroa vacciniforme (HV) is a rare form of photosensitivity disorder in children and is frequently associated with Epstein–Barr virus (EBV) infection, whereas HV-like lymphoproliferative disorders (HVLPD) describe a spectrum of EBV-associated T-cell or natural killer (NK)-cell lymphoproliferations with HV-like cutaneous manifestations, including EBV-positive HV, atypical HV, and HV-like lymphoma. Classic HV occurs in childhood with papulovesicules on sun-exposed areas, which is usually induced by sunlight and ultraviolet irradiation, and mostly resolves by early adult life. Unlike classic HV, atypical or severe HV manifests itself as recurrent papulovesicular eruptions in sun-exposed and sun-protected areas associated occasionally with facial edema, fever, lymphadenopathy, oculomucosal lesions, gastrointestinal involvement, and hepatosplenomegaly. Notably, atypical or severe HV may progress to EBV-associated systemic T-cell or natural killer (NK)-cell lymphoma after a chronic course. Although rare in the United States and Europe, atypical or severe HV and HV-like lymphoma are predominantly reported in children from Asia and Latin America with high EBV DNA levels, low numbers of NK cells, and T cell clones in the blood. In comparison with the conservative treatment used for patients with classic HV, systemic therapy such as immunomodulatory agents is recommended as the first-line therapy for patients with atypical or severe HV. This review aims to provide an integrated overview of current evidence and knowledge of HV and HVLPD to elucidate the pathophysiology, practical issues, environmental factors, and the impact of EBV infection.

scholarly journals Natural Killer Cell Responses during Human γ-Herpesvirus Infections

Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 655
Author(s):  
Christian Münz
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Epstein Barr Virus ◽  
Nk Cell ◽  
Killer Cell ◽  
Kaposi Sarcoma ◽  
Antibody Dependent Cellular Cytotoxicity ◽  
Barr Virus ◽  
Cell Responses ◽  
Epstein Barr

Herpesviruses are main sculptors of natural killer (NK) cell repertoires. While the β-herpesvirus human cytomegalovirus (CMV) drives the accumulation of adaptive NKG2C-positive NK cells, the human γ-herpesvirus Epstein–Barr virus (EBV) expands early differentiated NKG2A-positive NK cells. While adaptive NK cells support adaptive immunity by antibody-dependent cellular cytotoxicity, NKG2A-positive NK cells seem to preferentially target lytic EBV replicating B cells. The importance of this restriction of EBV replication during γ-herpesvirus pathogenesis will be discussed. Furthermore, the modification of EBV-driven NK cell expansion by coinfections, including by the other human γ-herpesvirus Kaposi sarcoma-associated herpesvirus (KSHV), will be summarized.

Characterization of novel natural killer (NK)–cell and γδ T-cell lines established from primary lesions of nasal T/NK-cell lymphomas associated with the Epstein-Barr virus

Blood ◽  
2001 ◽  
Vol 97 (3) ◽  
pp. 708-713 ◽  
Author(s):  
Hiroshi Nagata ◽  
Akiyoshi Konno ◽  
Nobuhiro Kimura ◽  
Yu Zhang ◽  
Michiko Kimura ◽  
...  
Keyword(s):  
T Cell ◽  
Natural Killer ◽  
Cell Lines ◽  
Epstein Barr Virus ◽  
Nk Cell ◽  
Cell Phenotype ◽  
Γδ T Cell ◽  
Barr Virus ◽  
Genotypic Analysis ◽  
Epstein Barr

Abstract Studies on nasal T/natural killer (NK)–cell lymphoma have been hampered by its tendency to cause necrosis. Thus, the establishment of cell lines of this neoplasm would seem to be valuable. This study attempted to establish cell lines from primary lesions of this tumor, and successfully obtained 2 novel Epstein-Barr virus (EBV)–positive cell lines, SNK-6 and SNT-8, by means of high-dose recombinant interleukin 2. Flow cytometry showed that SNK-6 had an NK-cell phenotype, CD3−CD4−CD8−CD19−CD56+T-cell receptor (TCR) α/β− TCR γ/δ−, whereas SNT-8 was CD3+CD4−CD8−CD19−CD56+TCR α/β− TCR γ/δ+. These were consistent with immunophenotypes of their original tumors, and the cell lines had monoclonal EBV clones identical to ones in their original tumors. Thus, the cell lines developed from cells forming the primary lesions. Genotypic analysis showed that SNK-6 had unrearranged TCR and immunoglobulin heavy-chain genes, supporting the conclusion that SNK-6 was of NK-cell lineage. On the other hand, SNT-8 had rearranged TCR β-, γ-, and δ-chain genes, and together with its phenotype, SNT-8 proved to be a γδ T-cell line. This is the first report of the establishment of cell lines from primary lesions of nasal T/NK cell lymphomas, and the results demonstrated that there are at least 2 lineages, NK- and γδ T-cell, in this neoplasm. Moreover, it has been suggested that nasal T/NK cell lymphomas of these lineages may belong to the same clinicopathologic entity because both types of cases shared common clinical and histopathologic features.

scholarly journals Gntb-A, a Novel Sh2d1a-Associated Surface Molecule Contributing to the Inability of Natural Killer Cells to Kill Epstein-Barr Virus–Infected B Cells in X-Linked Lymphoproliferative Disease

2001 ◽  
Vol 194 (3) ◽  
pp. 235-246 ◽  
Author(s):  
Cristina Bottino ◽  
Michela Falco ◽  
Silvia Parolini ◽  
Emanuela Marcenaro ◽  
Raffaella Augugliaro ◽  
...  
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Epstein Barr Virus ◽  
Cell Activation ◽  
Nk Cell ◽  
Lymphoproliferative Disease ◽  
Sh2 Domain ◽  
Target Cells ◽  
Barr Virus ◽  
Epstein Barr

In humans, natural killer (NK) cell function is regulated by a series of receptors and coreceptors with either triggering or inhibitory activity. Here we describe a novel 60-kD glycoprotein, termed NTB-A, that is expressed by all human NK, T, and B lymphocytes. Monoclonal antibody (mAb)-mediated cross-linking of NTB-A results in the induction of NK-mediated cytotoxicity. Similar to 2B4 (CD244) functioning as a coreceptor in the NK cell activation, NTB-A also triggers cytolytic activity only in NK cells expressing high surface densities of natural cytotoxicity receptors. This suggests that also NTB-A may function as a coreceptor in the process of NK cell activation. Molecular cloning of the cDNA coding for NTB-A molecule revealed a novel member of the immunoglobulin superfamily belonging to the CD2 subfamily. NTB-A is characterized, in its extracellular portion, by a distal V-type and a proximal C2-type domain and by a cytoplasmic portion containing three tyrosine-based motifs. NTB-A undergoes tyrosine phosphorylation and associates with the Src homology 2 domain–containing protein (SH2D1A) as well as with SH2 domain–containing phosphatases (SHPs). Importantly, analysis of NK cells derived from patients with X-linked lymphoproliferative disease (XLP) showed that the lack of SH2D1A protein profoundly affects the function not only of 2B4 but also of NTB-A. Thus, in XLP-NK cells, NTB-A mediates inhibitory rather than activating signals. These inhibitory signals are induced by the interaction of NTB-A with still undefined ligands expressed on Epstein-Barr virus (EBV)-infected target cells. Moreover, mAb-mediated masking of NTB-A can partially revert this inhibitory effect while a maximal recovery of target cell lysis can be obtained when both 2B4 and NTB-A are simultaneously masked. Thus, the altered function of NTB-A appears to play an important role in the inability of XLP-NK cells to kill EBV-infected target cells.

scholarly journals Hydroa Vacciniforme and Hydroa Vacciniforme-like Lymphoproliferative Disorder: A Spectrum of Disease Phenotypes Associated with Ultraviolet Irradiation and Chronic Epstein-Barr Virus Infection

2020 ◽  
Author(s):  
Chien-Chin Chen ◽  
Kung-Chao Chang ◽  
L. Jeffrey Medeiros ◽  
Julia Yu-Yun Lee
Keyword(s):  
T Cell ◽  
Ultraviolet Irradiation ◽  
Epstein Barr Virus ◽  
Nk Cell ◽  
The United States ◽  
Current Evidence ◽  
Barr Virus ◽  
Ebv Infection ◽  
Hydroa Vacciniforme ◽  
Epstein Barr

Hydroa vacciniforme (HV) is a rare form of photosensitivity disorders in children and is frequently associated with Epstein-Barr virus (EBV) infection, whereas HV-like lymphoproliferative disorders (HVLPD) describe a spectrum of EBV-associated T-cell or NK-cell lymphoproliferations with HV-like cutaneous manifestations, including EBV-positive HV, atypical HV, and HV-like lymphoma. Classic HV occurs in childhood with vesiculopapules on sun-exposed areas, which is usually induced by sunlight and ultraviolet irradiation, and mostly resolves by early adult life. Unlike classic HV, atypical or severe HV manifests itself as recurrent papulovesicular eruptions in sun-exposed and sun-protected areas associated occasionally with facial edema, fever, lymphadenopathy, oculomucosal lesions, gastrointestinal involvement, and hepatosplenomegaly. Notably, atypical or severe HV may progress to EBV-associated systemic T-cell or natural killer (NK)-cell lymphoma after a chronic course. Although rare in the United States and Europe, atypical or severe HV and HV-like lymphoma are predominantly reported in children from Asia and Latin America with high EBV DNA levels, low numbers of NK cells, and T cell clones in the blood. In comparison with the conservative treatment used for patients with classic HV, systemic therapy such as immunomodulatory therapy is recommended as the first-line therapy for patients with atypical or severe HV. This review aims to provide an integrated, overview of current evidence and knowledge of HV and HVLPD to elucidate the pathophysiology, practical issues, environmental factors, and the impact of EBV infection.

scholarly journals Patients With Natural Killer (NK) Cell Chronic Active Epstein-Barr Virus Have Immature NK Cells and Hyperactivation of PI3K/Akt/mTOR and STAT1 Pathways

2020 ◽  
Vol 222 (7) ◽  
pp. 1170-1179
Author(s):  
Matthew K Howe ◽  
Kennichi Dowdell ◽  
Hye Sun Kuehn ◽  
Qingxue Li ◽  
Geoffrey T Hart ◽  
...  
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Epstein Barr Virus ◽  
Nk Cell ◽  
Cell Phenotype ◽  
Jak Inhibitors ◽  
Barr Virus ◽  
Phosphorylated Akt ◽  
Epstein Barr

Abstract Background Chronic active Epstein-Barr virus (CAEBV) presents with high levels of viral genomes in blood and tissue infiltration with Epstein-Barr virus (EBV)–positive lymphocytes. The pathogenesis of CAEBV is poorly understood. Methods We evaluated 2 patients with natural killer (NK) cell CAEBV and studied their NK cell phenotype and signaling pathways in cells. Results Both patients had increased numbers of NK cells, EBV predominantly in NK cells, and immature NK cells in the blood. Both patients had increased phosphorylation of Akt, S6, and STAT1 in NK cells, and increased total STAT1. Treatment of 1 patient with sirolimus reduced phosphorylation of S6 in T and B cells, but not in NK cells and did not reduce levels of NK cells or EBV DNA in the blood. Treatment of both patients’ cells with JAK inhibitors in vitro reduced phosphorylated STAT1 to normal. Patients with T- or B-cell CAEBV had increased phosphorylation of Akt and S6 in NK cells, but no increase in total STAT1. Conclusions The increase in phosphorylated Akt, S6, and STAT1, as well as immature NK cells describe a new phenotype for NK cell CAEBV. The reduction of STAT1 phosphorylation in their NK cells with JAK inhibitors suggests a novel approach to therapy.

scholarly journals Evidence for Early Infection of Nonneoplastic Natural Killer Cells by Epstein-Barr Virus

2002 ◽  
Vol 76 (21) ◽  
pp. 11139-11142 ◽  
Author(s):  
Pascal Trempat ◽  
Julie Tabiasco ◽  
Pascale Andre ◽  
Nathalie Faumont ◽  
Fabienne Meggetto ◽  
...  
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Epstein Barr Virus ◽  
Early Event ◽  
Specific Marker ◽  
Barr Virus ◽  
Ebv Infection ◽  
Latently Infected ◽  
Epstein Barr ◽  
Combined Detection

ABSTRACT We examined lymph nodes and tonsils from patients with infectious mononucleosis by combined detection of EBV-encoded RNA and a specific marker of natural killer (NK) cells, PEN5. A small number of Epstein-Barr virus (EBV) latently infected nonneoplastic NK cells were detected. Our data demonstrate that NK cells are natural targets of EBV and that infection of these cells is an early event observed during primary EBV infection.

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