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

Benjamin Wizel, Barry C. Starcher, Buka Samten, Zissis Chroneos, Peter F. Barnes, John Dzuris, Yuichiro Higashimoto, Ettore Appella, Alessandro Sette

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49 Scopus citations

Abstract

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-2b 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.

Original languageEnglish (US)
Pages (from-to)2524-2535
Number of pages12
JournalJournal of Immunology
Volume169
Issue number5
DOIs
StatePublished - Sep 1 2002

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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    Wizel, B., Starcher, B. C., Samten, B., Chroneos, Z., Barnes, P. F., Dzuris, J., Higashimoto, Y., Appella, E., & Sette, A. (2002). Multiple Chlamydia pneumoniae antigens prime CD8+ Tc1 responses that inhibit intracellular growth of this vacuolar pathogen. Journal of Immunology, 169(5), 2524-2535. https://doi.org/10.4049/jimmunol.169.5.2524