Development of moleculartargeted therapy for EBV-infected NK cell lymphocytosis in the patients with hypersensitivity to mosquito bites

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Hypersensitivity to mosquito bites (HMB) is characterized by intense local skin symptoms, which consist of not only erythema or bulla but also ulceration or scarring, and systemic symptoms such as high fever, lymphadenopathy, and hepatosplenomegaly. The patients with lymphoproliferation of EB virus (EBV) -infected NK/T cells, including NK/T cell leukemia/lymphoma, often show the clinical manifestation of HMB. We have demonstrated that mosquito bites can induce expression of the viral oncogene LMP1 in NK cells via mosquito antigen-specific CD4^+ T cells, which may be involved in the proliferation of NK cells. The purpose of our present study is to design specific siRNA against LMP1, and transfer the siRNA into EBV-infected NK/T cells to investigate a function of LMP1 in EBV-infected NK/T cell proliferation. The goal of this study is to develop the molecular-targeted therapy for EBV-infected NK cell lymphocytosis in the patients with HMB. At first, we decided the optimum condition of siRNA transfection into lymphocytes using Oligofectamine. Next, we designed the candidates of LMP1-siRNA, and transfer them into EBV-infected NK/T cells. However, the inhibition effect of LMP1 mRNA expression by the LMP1-siRNA is poorly reproducible. After changing the transfection reagent to PrimaPort (CREDIA JAPAN), the transfection efficiency was improved, and the LMP1-siRNA significantly inhibited LMP1 mRNA expression, but did not suppress EBV-infected NK/T cell proliferation.