title: Mosquito salivary gland extracts induce EBV-infected NK cell oncogenesis via CD4 T cells in patients with hypersensitivity to mosquito bites.
abstract: Severe hypersensitivity to mosquito bites (HMB) is characterized by intense local skin reactions and systemic symptoms such as high fever, lymphadenopathy, and hepatosplenomegaly. Patients with HMB often have natural killer (NK) cell lymphocytosis associated with Epstein-Barr virus (EBV) infection. Here we investigated whether mosquito bites have any influence on the oncogenesis of EBV-infected NK cells. We examined six HMB patients with EBV-infected NK cell lymphocytosis. We first demonstrated that CD4+ T cells, but not NK cells, proliferated well in response to mosquito salivary gland extracts (SGE), especially to SGE of Aedes albopictus. When NK cells were cocultured with autologous CD4+ T cells stimulated by mosquito SGE, the expression of viral oncogene latent membrane protein 1 (LMP1) was remarkably enhanced. Next, we stimulated mononuclear cells of the patients with mosquito SGE, and NK cell counts were monitored for 28 d. The counts changed little from initial levels in the culture with mosquito SGE, whereas they decreased steadily in the culture without the extracts. Furthermore, we detected LMP1 mRNA in the skin lesion induced by mosquito SGE. These results suggest that mosquito bites can induce expression of the viral oncogene LMP1 in NK cells via mosquito antigen-specific CD4+ T cells, which is involved in the oncogenesis of NK cells in vivo.
authors.affiliation: Department of Dermatology, Nara Medical University School of Medicine, Karshihara, Japan. asadah@naramed-u.ac.jp
authors.forename: Hideo
authors.initials: H
authors.lastname: Asada
authors.forename: Mamiko
authors.initials: M
authors.lastname: Saito-Katsuragi
authors.forename: Hironori
authors.initials: H
authors.lastname: Niizeki
authors.forename: Akira
authors.initials: A
authors.lastname: Yoshioka
authors.forename: Setsuo
authors.initials: S
authors.lastname: Suguri
authors.forename: Masaaki
authors.initials: M
authors.lastname: Isonokami
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Aoki
authors.forename: Shigehiko
authors.initials: S
authors.lastname: Ishihara
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Tokura
authors.forename: Keiji
authors.initials: K
authors.lastname: Iwatsuki
authors.forename: Sachiko
authors.initials: S
authors.lastname: Miyagawa
mesh_terms: D000293:Adolescent; D000330:Aedes / Q000276:immunology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002457:Cell Extracts / Q000494:pharmacology; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D018920:Coculture Techniques; D020031:Epstein-Barr Virus Infections / Q000150:complications* / Q000276:immunology / Q000821:virology; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D006967:Hypersensitivity / Q000150:complications* / Q000276:immunology; D007223:Infant; D007299:Insect Bites and Stings / Q000150:complications* / Q000276:immunology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000821:virology*; D008218:Lymphocytosis / Q000209:etiology* / Q000276:immunology / Q000821:virology; D008297:Male; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D012469:Salivary Glands / Q000276:immunology; D012867:Skin / Q000737:chemistry; D014763:Viral Matrix Proteins / Q000235:genetics
chemical_list: D002457:Cell Extracts; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D012333:RNA, Messenger; D014763:Viral Matrix Proteins