Gamma Interferon Production by Cytotoxic T Lymphocytes Is Required for Resolution of Chlamydia trachomatis Infection

In this study, we used mice in which the gene for gamma interferon (IFN-γ) has been disrupted (IFN-γ(−/−) mice) to study the role of this cytokine in the resolution of Chlamydia trachomatis infection. We show that IFN-γ(−/−) mice are impaired in the ability to clear infection with C. trachomatis compared to IFN-γ(+/+) control mice. Activated CD8(+) cytotoxic T lymphocytes (CTL) secrete IFN-γ in response to intracellular infection, and we have shown previously that a Chlamydia-specific CTL line can reduce C. trachomatis infection when adoptively transferred into infected mice. In the present study, we found that when these IFN-γ(+/+) CTL lines are transferred into Chlamydia-infected IFN-γ(−/−) mice, the transferred CTL cannot overcome the immune defect seen in the IFN-γ(−/−) mice. We also show that Chlamydia-specific CTL can be cultured from IFN-γ-deficient mice infected with C. trachomatis; however, the adoptive transfer of IFN-γ(−/−) CTL into infected IFN-γ(+/+) mice does not reduce the level of infection. These results suggest that IFN-γ production by CTL is not sufficient to overcome the defect that IFN-γ(−/−) mice have in the resolution of Chlamydia infection, yet IFN-γ production by CTL is required for the protective effect seen upon adoptive transfer of CTL into IFN-γ(+/+) mice.