Chlamydia muridarum-Specific CD4 T-Cell Clones Recognize Infected Reproductive Tract Epithelial Cells in an Interferon-Dependent Fashion

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Abstract
During natural infectionsChlamydia trachomatisurogenital serovars replicate predominantly in the epithelial cells lining the reproductive tract. This tissue tropism poses a unique challenge to host cellar immunity and future vaccine development. In the experimental mouse model, CD4 T cells are necessary and sufficient to clearChlamydia muridarumgenital tract infections. This implies that resolution of genital tract infection depends on CD4 T-cell interactions with infected epithelial cells. However, no laboratory has shown thatChlamydia-specific CD4 T cells can recognizeChlamydiaantigens presented by major histocompatibility complex class II (MHC-I) molecules on epithelial cells. In this report we show that MHC-II-restrictedChlamydia-specific CD4 T-cell clones recognize infected upper reproductive tract epithelial cells as early as 12 h postinfection. The timing of recognition and degree of T-cell activation are dependent on the interferon (IFN) milieu. Beta IFN (IFN-β) and IFN-γ have different effects on T-cell activation, with IFN-β blunting IFN-γ-induced upregulation of epithelial cell surface MHC-II and T-cell activation. Individual CD4 T-cell clones differed in their degrees of dependence on IFN-γ-regulated MHC-II for controllingChlamydiareplication in epithelial cells in vitro. We discuss our data as they relate to published studies with IFN knockout mice, proposing a straightforward interpretation of the existing literature based on CD4 T-cell interactions with the infected reproductive tract epithelium.