Antigen-Specific CD4 T Cell-Derived Gamma Interferon Is Both Necessary and Sufficient for Clearing from the Small Intestine but Not the Large Intestine.

The genital tract pathogen is frequently detected in the gastrointestinal tract, but the host immunity that regulates chlamydial colonization in the gut remains unclear. In a -C57 mouse model, chlamydial organisms are cleared from the genital tract in ∼4 weeks, but the genital organisms can spread to the gastrointestinal tract. We found that the gastrointestinal chlamydial organisms were cleared from the small intestine by day 28, paralleling their infection course in the genital tract, but persisted in the large intestine for long periods. Mice deficient in α/β T cells or CD4 T cells but not CD8 T cells showed chlamydial persistence in the small intestine, indicating a critical role for CD4 T cells in clearing from the small intestine. The CD4 T cell-dependent clearance is likely mediated by gamma interferon (IFN-γ), since mice deficient in IFN-γ but not interleukin 22 (IL-22) signaling pathways rescued chlamydial colonization in the small intestine. Furthermore, exogenous IFN-γ was sufficient for clearing from the small intestine but not the large intestine. Mice deficient in developing -specific Th1 immunity showed chlamydial persistence in the small intestine. Finally, IFN-γ-producing CD4 but not CD8 T cells from immunized donor mice were sufficient for eliminating from the small intestine but not the large intestine of recipient mice. Thus, we have demonstrated a critical role for Th1 immunity in clearing from the small intestine but not the large intestine, indicating that chlamydial colonization in different regions of the gastrointestinal tract is regulated by distinct immune mechanisms.