Chlamydia muridarum-specific CD4 T-cell clones recognize infected reproductive tract epithelial cells in an interferon-dependent fashion.
During natural infections Chlamydia trachomatis urogenital 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 clear Chlamydia muridarum genital 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 that Chlamydia-specific CD4 T cells can recognize Chlamydia antigens presented by major histocompatibility complex class II (MHC-I) molecules on epithelial cells. In this report we show that MHC-II-restricted Chlamydia-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-beta) and IFN-gamma have different effects on T-cell activation, with IFN-beta blunting IFN-gamma-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-gamma-regulated MHC-II for controlling Chlamydia replication 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.
Jayarapu
Krupakar
K
Division of Infectious Diseases, Department of Medicine, Indiana University School of Medicine, 545 Barnhill Drive, #435, Indianapolis, IN 46202, USA.
Kerr
Micah S
MS
Katschke
Adrian
A
Johnson
Raymond M
RM
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D023502:Chlamydia muridarum / Q000276:immunology*; D004847:Epithelial Cells / Q000382:microbiology*; D005260:Female; D006801:Humans; D007372:Interferons / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D014551:Urinary Tract / Q000276:immunology* / Q000382:microbiology*
D007372:Interferons