title: Immunization with live and dead Chlamydia muridarum induces different levels of protective immunity in a murine genital tract model: correlation with MHC class II peptide presentation and multifunctional Th1 cells.
abstract: Mice that were intranasally vaccinated with live or dead Chlamydia muridarum with or without CpG-containing oligodeoxynucleotide 1862 elicited widely disparate levels of protective immunity to genital tract challenge. We found that the frequency of multifunctional T cells coexpressing IFN-γ and TNF-α with or without IL-2 induced by live C. muridarum most accurately correlated with the pattern of protection against C. muridarum genital tract infection, suggesting that IFN-γ(+)-producing CD4(+) T cells that highly coexpress TNF-α may be the optimal effector cells for protective immunity. We also used an immunoproteomic approach to analyze MHC class II-bound peptides eluted from dendritic cells (DCs) that were pulsed with live or dead C. muridarum elementary bodies (EBs). We found that DCs pulsed with live EBs presented 45 MHC class II C. muridarum peptides mapping to 13 proteins. In contrast, DCs pulsed with dead EBs presented only six MHC class II C. muridarum peptides mapping to three proteins. Only two epitopes were shared in common between the live and dead EB-pulsed groups. This study provides insights into the role of Ag presentation and cytokine secretion patterns of CD4(+) T effector cells that correlate with protective immunity elicited by live and dead C. muridarum. These insights should prove useful for improving vaccine design for Chlamydia trachomatis.
authors.affiliation: British Columbia Centre for Disease Control, University of British Columbia, Vancouver, British Columbia V5Z 4R4, Canada.
authors.forename: Hong
authors.initials: H
authors.lastname: Yu
authors.forename: Karuna P
authors.initials: KP
authors.lastname: Karunakaran
authors.forename: Isabelle
authors.initials: I
authors.lastname: Kelly
authors.forename: Caixia
authors.initials: C
authors.lastname: Shen
authors.forename: Xiaozhou
authors.initials: X
authors.lastname: Jiang
authors.forename: Leonard J
authors.initials: LJ
authors.lastname: Foster
authors.forename: Robert C
authors.initials: RC
authors.lastname: Brunham
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D002690:Chlamydia Infections / Q000276:immunology* / Q000517:prevention & control; D023502:Chlamydia muridarum / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity; D004195:Disease Models, Animal; D005260:Female; D006367:HeLa Cells; D000949:Histocompatibility Antigens Class II / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular; D002479:Inclusion Bodies / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology* / Q000382:microbiology; D014623:Vaginal Diseases / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control
chemical_list: D001428:Bacterial Vaccines; D000949:Histocompatibility Antigens Class II; D010455:Peptides