title: Disordered expression of inhibitory receptors on the NK1-type natural killer (NK) leukaemic cells from patients with hypersensitivity to mosquito bites.
abstract: Recent studies have revealed the existence of a distinct type of NK cell leukaemia of the juvenile type, which presents with hypersensitivity to mosquito bites (HMB) as an essential clinical manifestation and is infected with clonal Epstein-Barr virus (EBV). This disorder is thus called HMB-EBV-NK disease and has been reported in Orientals, mostly from Japan. We investigated the profile of cytokine production and the expression of both types of NK inhibitory receptors, i.e. CD94 lectin-like dimers and killer-cell immunoglobulin-like receptors, in NK leukaemic cells from three patients with HMB-EBV-NK disease. It was found that freshly isolated NK leukaemic cells expressed mRNA for interferon-gamma (IFN-gamma) and additionally produced IL-10 upon stimulation with IL-2, indicating that the NK cells were of NK1 type. More than 98% of NK cells from the patients bore CD94 at a higher level than did normal NK cells, whereas p70 or NKAT2, belonging to immunoglobulin-like receptor, was not expressed in those NK cells. Freshly isolated leukaemic NK cells transcribed mRNA for CD94-associated molecule NKG2C at an abnormally high level, and upon stimulation with IL-2 and/or IL-12 they expressed NKG2A as well. The disordered expression of these inhibitory receptors not only provides some insights into the pathogenesis of HMB-EBV-NK disease but also can be used as phenotypic markers for the diagnosis of this type of NK cell leukaemia.
authors.affiliation: Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan. seo445@hama-med.ac.jp
authors.forename: N
authors.initials: N
authors.lastname: Seo
authors.forename: Y
authors.initials: Y
authors.lastname: Tokura
authors.forename: S
authors.initials: S
authors.lastname: Ishihara
authors.forename: Y
authors.initials: Y
authors.lastname: Takeoka
authors.forename: S
authors.initials: S
authors.lastname: Tagawa
authors.forename: M
authors.initials: M
authors.lastname: Takigawa
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis*; D002478:Cells, Cultured; D009033:Culicidae; D020031:Epstein-Barr Virus Infections / Q000150:complications* / Q000276:immunology; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000150:complications / Q000276:immunology*; D007299:Insect Bites and Stings / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000494:pharmacology; D007564:Japan; D007694:Killer Cells, Natural / Q000276:immunology*; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D011971:Receptors, Immunologic / Q000096:biosynthesis*; D011975:Receptors, Mitogen / Q000096:biosynthesis*; D055607:Receptors, Natural Killer Cell
chemical_list: D015703:Antigens, CD; D007376:Interleukin-2; C527054:KLRC1 protein, human; C527059:KLRC2 protein, human; C497869:KLRD1 protein, human; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D011971:Receptors, Immunologic; D011975:Receptors, Mitogen; D055607:Receptors, Natural Killer Cell; D016753:Interleukin-10; D007371:Interferon-gamma