title: CD4⁺ T-cell immunity in the female genital tract is critically dependent on local mucosal immunization.
abstract: Immunizations via the i.n. and intravaginal (ivag) routes effectively generate strong genital tract antibody-mediated immunity. To what extent the same is true for T-cell responses is incompletely known. Therefore, we set out to investigate optimal conditions for stimulation of genital tract CD4(+)  T-cell responses, using adoptive transfer of mouse DO11.10 TCR transgenic T cells specific for OVA and OVA conjugated to cholera toxin (CT) as an immunogen. We observed that progesterone was required for a T-cell response following ivag immunization, whereas estradiol prevented a response. Although i.n. immunization stimulated OVA-specific CD4(+)  T-cell responses in the draining LNs, it was substantially less effective compared to ivag. More importantly, an ivag booster immunization was absolutely required to attract T cells to the genital tract mucosa itself. While clinical use of CT is precluded because of its toxicity, we developed a combined adjuvant vector based on a non-toxic derivative of CT and immune-stimulating complexes. The CTA1-DD/immune-stimulating complexes (ISCOMs) adjuvant together with major outer membrane protein was effective at stimulating genital tract CD4(+)  T-cell immunity and protection against a live chlamydial infection, which holds promise for the development of mucosal vaccines against sexually transmitted infections.
authors.affiliation: Department of Microbiology and Immunology, Mucosal Immunobiology and Vaccine Center, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Ellen
authors.initials: E
authors.lastname: Marks
authors.forename: Anja
authors.initials: A
authors.lastname: Helgeby
authors.forename: Jan O
authors.initials: JO
authors.lastname: Andersson
authors.forename: Karin
authors.initials: K
authors.lastname: Schön
authors.forename: Nils Y
authors.initials: NY
authors.lastname: Lycke
mesh_terms: D000282:Administration, Intravaginal; D019264:Adoptive Transfer; D000818:Animals; D000941:Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000008:administration & dosage; D004958:Estradiol / Q000008:administration & dosage; D005260:Female; D005836:Genitalia, Female / Q000473:pathology*; D006801:Humans; D018928:Immunity, Mucosal / Q000187:drug effects / Q000235:genetics; D007117:Immunization, Secondary; D008213:Lymphocyte Activation / Q000187:drug effects / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D011374:Progesterone / Q000008:administration & dosage
chemical_list: D000941:Antigens; D011374:Progesterone; D004958:Estradiol; D010047:Ovalbumin; D002772:Cholera Toxin