T Cell Responses in the Absence of IFN-γ Exacerbate Uterine Infection with Chlamydia trachomatis

Abstract

Infection with the obligate intracellular bacterium Chlamydia trachomatis is controlled primarily by IFN-γ and Th1 immunity. In this study, we used cells from a Chlamydia-specific CD4⁺ TCR-transgenic mouse to assess the role of IFN-γ in development of Th1 immunity. We show that secretion of host IFN-γ or the ability of host cells to respond to secreted IFN-γ is not required to initiate a Th1 immune response. Additionally, we found that Ag-specific CD4⁺ cells that were preskewed toward Th1 confer protection, whereas cells preskewed toward Th2 cause a previously unreported exacerbation of disease leading to higher bacterial load. Chlamydia-specific Th1 cells transferred into an IFN-γ^−/− recipient mouse demonstrate protective effects, but the same cells exacerbate bacterial burden when transferred into IFN-γR^−/− mice. Thus, we demonstrate that the secretion of IFN-γ is necessary for protection against C. trachomatis and that in the absence of host cell IFN-γR expression, both Th1 and Th2 cells lead to increased burden of C. trachomatis.