title: An atypical CD8 T-cell response to Chlamydia muridarum genital tract infections includes T cells that produce interleukin-13.
abstract: Chlamydia trachomatis urogenital serovars D-K are intracellular bacterial pathogens that replicate almost exclusively in human reproductive tract epithelium. In the C. muridarum mouse model for human Chlamydia genital tract infections CD4 T helper type 1 cell responses mediate protective immunity while CD8 T-cell responses have been associated with scarring and infertility. Scarring mediated by CD8 T cells requires production of tumour necrosis factor-α (TNF-α); however, TNF-α is associated with protective immunity mediated by CD4 T cells. The latter result suggests that TNF-α in-and-of itself may not be the sole determining factor in immunopathology. CD8 T cells mediating immunopathology presumably do something in addition to producing TNF-α that is detrimental during resolution of genital tract infections. To investigate the mechanism underlying CD8 immunopathology we attempted to isolate Chlamydia-specific CD8 T-cell clones from mice that self-cleared genital tract infections. They could not be derived with antigen-pulsed irradiated naive splenocytes; instead derivation required use of irradiated immune splenocyte antigen-presenting cells. The Chlamydia-specific CD8 T-cell clones had relatively low cell surface CD8 levels and the majority were not restricted by MHC class Ia molecules. They did not express Plac8, and had varying abilities to terminate Chlamydia replication in epithelial cells. Two of the five CD8 clones produced interleukin-13 (IL-13) in addition to IL-2, TNF-α, IL-10 and interferon-γ. IL-13-producing Chlamydia-specific CD8 T cells may contribute to immunopathology during C. muridarum genital tract infections based on known roles of TNF-α and IL-13 in scar formation.
authors.affiliation: Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Raymond M
authors.initials: RM
authors.lastname: Johnson
authors.forename: Micah S
authors.initials: MS
authors.lastname: Kerr
authors.forename: James E
authors.initials: JE
authors.lastname: Slaven
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002690:Chlamydia Infections / Q000276:immunology* / Q000382:microbiology; D023502:Chlamydia muridarum / Q000276:immunology*; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000276:immunology / Q000382:microbiology; D005260:Female; D006801:Humans; D018793:Interleukin-13 / Q000096:biosynthesis* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D060737:Reproductive Tract Infections / Q000276:immunology* / Q000382:microbiology
chemical_list: D018793:Interleukin-13
keywords: CD8; Chlamydia; interleukin-13