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Induction of Interferon Alpha and Gamma from Human Lymphocytes by Dengue Virus-infected Cells

Division of Infectious Diseases, Department of Medicine, University of Massachusetts Medical Center, Worcester, Massachusetts 01605, U.S.A.
and¹ Division of Viral Products, National Institute for Biological Standards and Control, Holly Hill, Hampstead, London NW3 6RB, U.K.

Human peripheral blood lymphocytes (PBL) of non-immune donors produced interferon (IFN) when cultured with dengue virus-infected cells. IFN was detected as early as 2 h after exposure of PBL to dengue virus-infected cells, and the titres reached a maximum by 16 h of incubation. Dengue virus-infected cells treated with glutaraldehyde, which produced no infectious dengue virus, also induced IFN. These results indicate that PBL produce IFN in response to dengue virus-infected cells and that the production of IFN by PBL is due to stimulation of PBL by dengue virus-infected cells. Characterization of IFN-producing PBL with monoclonal antibodies demonstrated that the predominant producing cells were contained in M1⁺ and T3^- subsets, and that the Leu11⁺ subset contains some IFN-producing cells. The IFNs that were produced by the PBL exposed to dengue virus-infected cells were analysed by radioimmunoassay employing monoclonal antibodies specifically to detect IFN- or IFN-. IFN- as well as IFN- was produced by PBL exposed to dengue virus-infected cells. Both IFN- and IFN- were predominantly produced by PBL contained in M1⁺ and T3^- subsets. The observation that PBL of non-immune donors produced IFN- as well as IFN- in response to dengue virus-infected cells is of interest in view of the immunoregulatory roles of IFNs and the hypothesis that the complications of dengue virus infection (haemorrhagic fever and shock) may be due to immunopathology.

Keywords: dengue virus, interferon, natural killer cells

Received 19 November 1985; accepted 17 April 1986.

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