CD40 ligand-deficient mice generate a normal primary cytotoxic T- lymphocyte response but a defective humoral response to a viral infection

Jason K. Whitmire, Mark K. Slifka, Iqbal S. Grewal, Richard A. Flavell, Rafi Ahmed

    Research output: Contribution to journalArticle

    128 Scopus citations

    Abstract

    CD40 ligand is expressed on activated T cells and interacts with CD40 on B cells and monocytes. It is not known what role CD40 ligand plays in the generation of immune responses to viral infection. To address this issue, we examined virus-specific T- and B-cell responses in CD40 ligand-deficient (CD40L-/-) mice following infection with lymphocytic choriomeningitis virus (LCMV). We found that primary anti-LCMV specific antibody responses were severely impaired in CD40L-/- mice, with the defect being most striking for antibody of the immunoglobulin G1 (IgG1) isotype. Interestingly, low levels of LCMV-specific antibodies of the IgG2a, IgG2b, and IgG3 isotypes were made in the CD40L-/- mice, showing that IgG1 responses are totally dependent on CD40L but that at least some IgG2a, IgG2b, and IgG3 responses can be CD40L independent. However, unlike CD40L+/+ mice, CD40L-/- mice were unable to sustain virus-specific antibody responses and showed a gradual decline in serum antibody levels over time. The CD40L-/- mice were also deficient in the generation of memory B cells. In contrast to the severely impaired humoral responses, CD40L-/- mice generated potent virus-specific CD8+ cytotoxic T- lymphocyte responses after LCMV infection and were able to clear the virus. These results show that CD40L does not play a rule in generating primary virus-specific CD8+ cytotoxic T-lymphocyte responses but does affect the primary antibody response and the generation of memory B cells.

    Original languageEnglish (US)
    Pages (from-to)8375-8381
    Number of pages7
    JournalJournal of virology
    Volume70
    Issue number12
    DOIs
    StatePublished - Dec 1996

    ASJC Scopus subject areas

    • Microbiology
    • Immunology
    • Insect Science
    • Virology

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