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-gamma-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-gamma and TNF-alpha, 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-gamma 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.
Wizel
Benjamin
B
Center for Pulmonary and Infectious Disease Control, Department of Microbiology and Immunology, University of Texas Health Center, Tyler 75708, USA. bwizel@uthct.edu
Starcher
Barry C
BC
Samten
Buka
B
Chroneos
Zissis
Z
Barnes
Peter F
PF
Dzuris
John
J
Higashimoto
Yuichiro
Y
Appella
Ettore
E
Sette
Alessandro
A
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement / Q000276:immunology; D023521:Chlamydophila Infections / Q000276:immunology / Q000382:microbiology; D016993:Chlamydophila pneumoniae / Q000254:growth & development* / Q000276:immunology* / Q000472:pathogenicity; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D006183:H-2 Antigens / Q000276:immunology / Q000378:metabolism; D064532:Histocompatibility Antigen H-2D; D007156:Immunologic Memory; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000378:metabolism; D007424:Intracellular Fluid / Q000276:immunology* / Q000382:microbiology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D016676:Macrophages, Alveolar / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009842:Oligopeptides / Q000276:immunology / Q000378:metabolism; D018410:Pneumonia, Bacterial / Q000276:immunology / Q000382:microbiology; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D013491:Suppressor Factors, Immunologic; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000382:microbiology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D014407:Tumor Cells, Cultured; D014617:Vacuoles / Q000276:immunology* / Q000382:microbiology
D000942:Antigens, Bacterial; D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D064532:Histocompatibility Antigen H-2D; D009842:Oligopeptides; D013491:Suppressor Factors, Immunologic; D007371:Interferon-gamma