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Human Interferon Alpha and Gamma Production by Lymphocytes During the Generation of Influenza Virus-specific Cytotoxic T Lymphocytes

¹ Division of Infectious Diseases, Department of Medicine, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, Massachusetts 01605, U.S.A.
and² Division of Virology, National Institute for Biological Standards and Control, Holly Hill, Hampstead, London NW3 6RB, U.K.

We analysed the production of interferons (IFN)-alpha and -gamma during the generation of human influenza-virus specific cytotoxic T lymphocyte (CTL) responses using monoclonal antibodies in a specific radioimmunoassay. The results showed that the peripheral blood mononuclear cells (PBM) of all donors tested produced IFN-gamma and had influenza A virus-specific CTL activity after stimulation. The amount of IFN-gamma produced and the level of CTL activity were significantly correlated. The PBM of some donors also produced IFN-alpha. The level of IFN-gamma produced was low during the first few days and increased subsequently, but IFN-alpha, when it was detected, was produced on day 1. The kinetics of the increase in IFN-gamma correlated with the increase in CTL activity. We also observed an increased percentage of cells bearing interleukin-2 receptors, which may have been a response to the production of IFN-gamma. The T cells active in lysing influenza A virus-infected target cells and in producing IFN-gamma were determined after separating effector cells with monoclonal antibodies. The CTL effector cells were mainly in the T8⁺ subset, but IFN-gamma-producing cells were found in both T4⁺ and T8⁺ subsets. These results suggest that influenza virus-specific T8⁺ CTL produce IFN-gamma in response to virus, and that T4⁺ cells which are not CTL effectors also produce IFN-gamma after restimulation with influenza A virus-infected cells.

Keywords: influenza virus, CTLs, interferon production

Received 3 April 1986; accepted 21 July 1986.

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