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    Poliovirus-spectfic CD4 + Thl Clones with Both Cytotoxic and Helper Activity Mediate Protective Humoral Immunity against a Lethal Poliovirus Infection in Transgenic Mice Expressing the Human Poliovirus Receptor


    Mahon, Bernard P. and Katrak, Kersi and Nomoto, Akio and Macadam, Andrew J. and Minor, Philip D. and Mills, Kingston H.G. (1995) Poliovirus-spectfic CD4 + Thl Clones with Both Cytotoxic and Helper Activity Mediate Protective Humoral Immunity against a Lethal Poliovirus Infection in Transgenic Mice Expressing the Human Poliovirus Receptor. Journal of Experimental Medicine, 181. pp. 1285-1292. ISSN 0022-1007

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    Abstract

    The current understanding of the function of CD4 + T helper (Th) cells in immunity to infectious diseases is that Thl cells, which secrete interleukin (IL)-2 and interferon-3,, induce cellular immune responses, whereas Th2 cells, which secrete IL-4, IL-5, IL-6, and IL-10, provide helper function for humoral immunity. We have used a panel of poliovirus-specific murine CD4 + T cell clones and mice transgenic for the human poliovirus receptor to evaluate the role of Th cell subpopulations in protective immunity to poliovirus. The majority of T cell clones, as well as polyclonal T cells generated from mice infected or immunized with poliovirus, secreted IL-2 and interferon-q,, but not IL-4, IL-5, or IL-10, a profile typical of Thl cells. The Thl clones displayed major histocompatibility complex class II-restricted cytotoxic T lymphocyte activity against specific poliovirus peptide-pulsed target ceils, but also provided help for antipoliovirus neutralizing antibody production. To examine the mechanism of immunity in vivo, we have used poliovirus receptor-transgenic mice on a BALB/c (H-2 a) background. These animals developed a poliomyelitis-like disease when challenged intravenously with a virulent wild-type strain of poliovirus, but not with an attenuated vaccine strain. Furthermore, mice immunized with the vaccine strain were protected against a subsequent challenge with wild-type virus. Using an adoptive transfer technique, we demonstrated that it was possible to confer protection with primed B cells in the presence of polyclonal poliovirus-specific T cells, but not when transgenic mice received either B cells or T cells alone. Furthermore, protection was observed when mice received primed B cells in the presence of a VP4-specific Thl clone. The findings demonstrate that Thl cells can mediate a protective immune response against poliovirus infection in vivo through helper activity for humoral immunity and that CD4 § T cells, specific for the internal poliovirus capsid protein, VP4, can provide effective help for a protective antibody response directed against surface capsid proteins.

    Item Type: Article
    Keywords: Poliovirus; CD4 + Thl Clones; Cytotoxic; Helper Activity; Humoral Immunity;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 7158
    Depositing User: Bernard Mahon
    Date Deposited: 05 Jul 2016 13:44
    Journal or Publication Title: Journal of Experimental Medicine
    Publisher: Rockefeller University Press
    Refereed: Yes
    URI:

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