RRC ID 38283
Author Suzuki D, Tsuji K, Yamamoto T, Fujii K, Iwatsuki K.
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.
Journal Exp. Hematol.
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.
MATERIALS AND 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.
Volume 38(10)
Pages 933-44
Published 2010-10
DOI 10.1016/j.exphem.2010.06.005
PII S0301-472X(10)00240-7
PMID 20600581
MeSH Adolescent Animals CD2 Antigens / immunology CD2 Antigens / metabolism Cell Line Culicidae / immunology Cytokines / immunology* Cytokines / metabolism Cytotoxicity, Immunologic / immunology Female Flow Cytometry Gene Expression / drug effects Herpesvirus 4, Human / genetics Herpesvirus 4, Human / immunology* Humans Hypersensitivity / etiology Hypersensitivity / immunology* Hypersensitivity / pathology Inflammation Mediators / immunology Inflammation Mediators / metabolism Insect Bites and Stings / complications Insect Bites and Stings / immunology* K562 Cells Killer Cells, Natural / immunology* Killer Cells, Natural / pathology Killer Cells, Natural / virology NK Cell Lectin-Like Receptor Subfamily B / immunology NK Cell Lectin-Like Receptor Subfamily B / metabolism Reverse Transcriptase Polymerase Chain Reaction Tetradecanoylphorbol Acetate / pharmacology Trans-Activators / genetics Tumor Necrosis Factor-alpha / metabolism Tumor Necrosis Factor-alpha / pharmacology
IF 2.436
Times Cited 3
WOS Category MEDICINE, RESEARCH & EXPERIMENTAL HEMATOLOGY
Resource
Human and Animal Cells