Anti-CD3 single-chain Fv/interleukin-18 fusion DNA induces anti-mycobacterial resistance via efficient interferon-γ production in BALB/c mice infected with Mycobacterium avium

Seung H. Kim, Daeho Cho, Tae S. Kim

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    1 Citation (Scopus)

    Abstract

    T helper type 1 (Th1) cell-mediated immune response performs a critical role in the induction of host defenses against a variety of intracellular pathogens. We recently demonstrated that the linkage between interleukin (IL)-18 and anti-CD3sFv genes confined the effect of IL-18 to the CD3+ T cells, resulting in the efficient induction of Thl immune responses. In this study, we attempted to determine whether the anti-CD3 single-chain Fv/IL-18 fusion DNA (pAnti-CD3sFv/IL-18) could stimulate resistance to Mycobacterium avium infection in genetically susceptible BALB/c mice. Immunization with pAnti-CD3sFv/IL-18 DNA during intranasal infection with M. avium resulted in a significant reduction in the bacterial load in the lung throughout the entire 10-week observation period. Immunization with pAnti-CD3sFv/IL-18 DNA induced and maintained significantly higher levels of cytotoxic activity and nitric oxide production by the lung cells, as compared with the injection of pAnti-CD3sFv DNA, or of a simple mixture of pAnti-CD3sFv DNA and pIL-18 DNA. Furthermore, the lung cells of the mice injected with pAnti-CD3sFv/IL-18 DNA exhibited persistent production of IFN-γ. Treatment with anti-IFN-γ antibody resulted in an abrogation of anti-mycobacterial effects in mice injected with pAnti-CD3sFv/IL-18 DNA. These results indicate that vaccination with the pAnti-CD3sFv/IL-18 fusion DNA induces significant resistance to M. avium infection, via the production of IFN-γ in CD4+ T cells.

    Original languageEnglish
    Pages (from-to)3365-3373
    Number of pages9
    JournalVaccine
    Volume24
    Issue number16
    DOIs
    Publication statusPublished - 2006 Apr 12

    Bibliographical note

    Funding Information:
    We would like to thank Dr. D.S. Lim, Dr. B.R. Blazar, and Dr. M.E. Reff for providing valuable reagents. This study was supported by a grant of the SRC/ERC program of the KOSEF/MOST (R11-2005-017-02001-0).

    Keywords

    • CD3 T cell
    • Fusion DNA
    • IL-18
    • Immunity
    • Mycobacterium avium

    ASJC Scopus subject areas

    • Molecular Medicine
    • General Immunology and Microbiology
    • General Veterinary
    • Public Health, Environmental and Occupational Health
    • Infectious Diseases

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