Multiple Chlamydia pneumoniae antigens prime CD8⁺ Tc1 responses that inhibit intracellular growth of this vacuolar pathogen

CD8⁺ T cells play an essential role in immunity to Chlamydia pneumoniae (Cpn). However, the target Ags recognized by Cpn-specific CD8⁺ T cells have not been identified, and the mechanisms by which this T cell subset contributes to protection remain unknown. In this work we demonstrate that Cpn infection primes a pathogen-specific CD8⁺ T cell response in mice. Eighteen H-2^b binding peptides representing sequences from 12 Cpn Ags sensitized target cells for MHC class I-restricted lysis by CD8⁺ CTL generated from the spleens and lungs of infected mice. Peptide-specific IFN-γ-secreting CD8⁺ T cells were present in local and systemic compartments after primary infection, and these cells expanded after pathogen re-exposure. CD8⁺ T cell lines to the 18 Cpn epitope-bearing peptides were cytotoxic, displayed a memory phenotype, and secreted IFN-γ and TNF-α but not IL-4. These CTL lines lysed Cpn-infected macrophages, and the lytic activity was inhibited by brefeldin A, indicating endogenous processing of CTL Ags. Finally, Cpn peptide-specific CD8⁺ CTL suppressed chlamydial growth in vitro by direct lysis of infected cells and by secretion of IFN-γ and other soluble factors. These studies provide information on the mechanisms by which CD8⁺ CTL protect against Cpn, furnish the tools to investigate their possible role in immunopathology, and lay the foundation for future work to develop vaccines against acute and chronic Cpn infections.