Characterization of Epstein-Barr virus (EBV)-infected natural killer (NK) cell proliferation in patients with severe mosquito allergy; establishment of an IL-2-dependent NK-like cell line.

The clinical evidence of a relationship between severe hypersensitivity to mosquito bite (HMB) and clonal expansion of EBV-infected NK cells has been accumulated. In order to clarify the mechanism of EBV-induced NK cell proliferation and its relationship with high incidence of leukaemias or lymphomas in HMB patients, we studied clonally expanded NK cells from three HMB patients and succeeded in establishing an EBV-infected NK-like cell line designated KAI3. Immunoblotting and reverse transcriptase-polymerase chain reaction (RT-PCR) analyses revealed that KAI3 cells as well as infected NK cells exhibited an EBV latent infection type II, where EBV gene expression was limited to EBNA 1 and LMP1. As KAI3 was established by culture with IL-2, IL-2 responsiveness of peripheral blood NK cells from patients was examined. The results represented markedly augmented IL-2-induced IL-2R alpha expression in NK cells. This characteristic property may contribute to the persistent expansion of infected NK cells. However, KAI3 cells as well as the NK cells from patients were not protected from apoptosis induced by either an anti-Fas antibody or NK-sensitive K562 cells. Preserved sensitivity to apoptosis might explain the relatively regulated NK cell numbers in the peripheral blood of the patients. To our knowledge, KAI3 is the first reported NK-like cell line established from patients of severe chronic active EBV infection (SCAEBV) before the onset of leukaemias or lymphomas. KAI3 cells will contribute to the study of EBV persistency in the NK cell environment and its relationship with high incidence of leukaemias or lymphomas in HMB patients.