Disordered expression of inhibitory receptors on the NK1-type natural killer (NK) leukaemic cells from patients with hypersensitivity to mosquito bites

Recent studies have revealed the existence of a distinct type of NK cell le ukaemia of the juvenile type, which presents with hypersensitivity to mosqu ito bites (HMB) as an essential clinical manifestation and is infected with clonal Epstein-Barr virus (EBV). This disorder is thus called HMB-EBV-NK d isease and has been reported in Orientals, mostly from Japan. We investigat ed the profile of cytokine production and the expression of both types of N K inhibitory receptors, i.e. CD94 lectin-like dimers and killer-cell immuno globulin-like receptors, in NK leukaemic cells from three patients with HMB -EBV-NK disease. It was found that freshly isolated NK leukaemic cells expr essed 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 th an did normal NK cells, whereas p70 or NKAT2, belonging to immunoglobulin-l ike receptor, was not expressed in those NK cells. Freshly isolated leukaem ic NK cells transcribed mRNA for CD94-associated molecule NRG2C at an abnor mally high level, and upon stimulation with IL-2 and/or IL-12 they expresse d NKG2A as well. The disordered expression of these inhibitory receptors no t only provides some insights into the pathogenesis of HMB-EBV-NK disease b ut also can be used as phenotypic markers for the diagnosis of this type of NK cell leukaemia.