title: Suppression of endogenous IL-10 gene expression in dendritic cells enhances antigen presentation for specific Th1 induction: potential for cellular vaccine development.
abstract: A new paradigm for designing vaccines against certain microbial pathogens, including Chlamydia trachomatis, is based on the induction of local mucosal Th1 response. IL-10 is an anti-inflammatory cytokine that exerts negative immunoregulatory influence on Th1 response. This study investigated whether biochemical modulation of endogenous IL-10 expression at the level of APCs is a practical strategy for enhancing the specific Th1 response against pathogens controlled by Th1 immunity. The results revealed that the high resistance of genetically engineered IL-10-/- (IL-10KO) mice to genital chlamydial infection is a function of the predilection of their APCs to rapidly and preferentially activate a high Th1 response. Thus, in microbiological analysis, IL-10KO mice suffered a shorter duration of infection, less microbial burden, and limited ascending infection than immunocompetent wild-type mice. Also, IL-10KO were resistant to reinfection after 8 wk of the primary infection. Cellular and molecular immunologic evaluation indicated that IL-10KO mice induced greater frequency of chlamydial-specific Th1 response following C. trachomatis infection. Moreover, IL-10KO APCs or antisense IL-10 oligonucleotide-treated wild-type APCs were potent activators of Th1 response from naive or immune T cells. Furthermore, both Ag-pulsed dendritic cells from IL-10KO mice and IL-10 antisense-treated dendritic cells from wild-type mice were efficient cellular vaccines in adoptive immunotherapeutic vaccination against genital chlamydial infection. These findings may furnish a novel immunotherapeutic strategy for boosting the Th1 response against T cell-controlled pathogens and tumors, using IL-10-deficient APCs as vaccine delivery agents.
authors.affiliation: Department of Microbiology and Immunology, Morehouse School of Medicine, Atlanta, GA 30310, USA.
authors.forename: J U
authors.initials: JU
authors.lastname: Igietseme
authors.forename: G A
authors.initials: GA
authors.lastname: Ananaba
authors.forename: J
authors.initials: J
authors.lastname: Bolier
authors.forename: S
authors.initials: S
authors.lastname: Bowers
authors.forename: T
authors.initials: T
authors.lastname: Moore
authors.forename: T
authors.initials: T
authors.lastname: Belay
authors.forename: F O
authors.initials: FO
authors.lastname: Eko
authors.forename: D
authors.initials: D
authors.lastname: Lyn
authors.forename: C M
authors.initials: CM
authors.lastname: Black
mesh_terms: D000276:Adjuvants, Immunologic / Q000235:genetics / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects / Q000235:genetics* / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology; D001428:Bacterial Vaccines / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D002690:Chlamydia Infections / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D020022:Genetic Predisposition to Disease; D006801:Humans; D016219:Immunotherapy, Adoptive; D016753:Interleukin-10 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics* / Q000627:therapeutic use; D008213:Lymphocyte Activation / Q000187:drug effects / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D002575:Uterine Cervicitis / Q000235:genetics / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D016585:Vaginosis, Bacterial / Q000235:genetics / Q000276:immunology / Q000517:prevention & control
chemical_list: D000276:Adjuvants, Immunologic; D001428:Bacterial Vaccines; D018984:Epitopes, T-Lymphocyte; D016376:Oligonucleotides, Antisense; D016753:Interleukin-10