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 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‐γ) 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.

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