Interferon-gamma and Effector Cell Activation are Required for Antibody-Mediated Immunity against Genital Chlamydia Infection

Abstract

Abstract Defining the mechanisms of immunity conferred by the combination of antibody and CD4+ T cells is fundamental to designing an efficacious chlamydial vaccine. Using the Chlamydia muridarum genital infection model of mice, which replicates many features of human C. trachomatis infection and avoids the characteristic low virulence of C. trachomatis in the mouse, we previously demonstrated a central role for antibody in immunity to chlamydial infection. We found that antibody alone was not protective. Instead, protection appeared to be conferred through an undefined antibody-cellular interaction. Using gene knockout mice and in vivo cellular depletion methods, antibody-mediated protection was shown to be solely dependent on the activation of an effector cell population in genital tract tissues by CD4+ T cells. Furthermore, the CD4+ T cell-secreted cytokine interferon-gamma (IFNγ) was found to be a key component of the protective antibody response. The function of IFNγ was not related to the immunoglobulin class or magnitude of the Chlamydia-specific antibody response or to recruitment of an effector cell population to genital tract tissue. Rather, IFNγ appears to be necessary for activation of the effector cell population that functions in antibody-mediated chlamydial immunity. Ongoing studies aim to identify the effector cell population(s) involved in the antibody-mediated protective response. Our results confirm the central role of antibody and CD4+ T cells in immunity to chlamydia reinfection, and demonstrate a key function for IFNγ in antibody-mediated protection.