title: Production of proinflammatory cytokines without invocation of cytotoxic effects by an Epstein-Barr virus-infected natural killer cell line established from a patient with hypersensitivity to mosquito bites.
abstract: OBJECTIVE
  Cumulative evidence supports that Epstein-Barr virus (EBV)-infected natural killer (NK) cells induce severe systemic and cutaneous inflammation in patients with hypersensitivity to mosquito bites (HMB). In order to understand the pathogenesis of HMB, we established an EBV-infected cell line and characterized the cytological profiles.
  
  
  METHODS
  A novel EBV-infected NK-cell line, designated NKED, was established from a patient with HMB and used for the present study along with two other NK-cell lines, KAI3 and KHYG-1.
  
  
  RESULTS
  NKED expressed the latency II-related transcripts. NKED cells were positive for CD2 and CD161 antigens, and negative for CD3, CD16, CD34, CD56, and T-cell receptor α/β and γ/δ antigens. Although NKED cells contained several cytotoxic molecules, the cells had an extremely poor cytotoxic activity. The majority of NKED cells were negative for perforin, major histocompatibility complex class I-restricted NK-cell receptors, CD94 and KIR2D, and an activating receptor, NKG2D. NKED cells, however, secreted higher levels of tumor necrosis factor-α. Stimulation with phorbol 12-myristate 13-acetate or tumor necrosis factor-α induced expression of BZLF1 messenger RNA in the NKED and KAI3 cells, indicating the transition from the latent- to the lytic-cycle infection.
  
  
  CONCLUSIONS
  These data suggested that NKED cells revealed a very low cytotoxic effect probably because of the low expression levels of perforin, but had the ability to release proinflammatory cytokines. NKED cells did not reflect the characteristics of HMB, as they were different from pathogenic NK cells proliferating in the HMB patient, but the difference indicated that pathogenic NK cells could change their character in the presence of interleukin-2.
authors.affiliation: Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. gmd14056@s.okayama-u.ac.jp
authors.forename: Daisuke
authors.initials: D
authors.lastname: Suzuki
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Tsuji
authors.forename: Takenobu
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Kazuyasu
authors.initials: K
authors.lastname: Fujii
authors.forename: Keiji
authors.initials: K
authors.lastname: Iwatsuki
mesh_terms: D000293:Adolescent; D000818:Animals; D018801:CD2 Antigens / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D009033:Culicidae / Q000276:immunology; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000276:immunology*; D006801:Humans; D006967:Hypersensitivity / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D007299:Insect Bites and Stings / Q000150:complications / Q000276:immunology*; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology / Q000821:virology; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015534:Trans-Activators / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology
chemical_list: C063676:BZLF1 protein, Herpesvirus 4, Human; D018801:CD2 Antigens; D016207:Cytokines; D018836:Inflammation Mediators; D055651:NK Cell Lectin-Like Receptor Subfamily B; D015534:Trans-Activators; D014409:Tumor Necrosis Factor-alpha; D013755:Tetradecanoylphorbol Acetate