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CD4⁺ T-cell immunity in the female genital tract is critically dependent on local mucosal immunization.
Marks, Ellen; Helgeby, Anja; Andersson, Jan O; Schön, Karin; Lycke, Nils Y.
Afiliação
  • Marks E; Department of Microbiology and Immunology, Mucosal Immunobiology and Vaccine Center, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
Eur J Immunol ; 41(9): 2642-53, 2011 Sep.
Article em En | MEDLINE | ID: mdl-21681740
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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Linfócitos T CD4-Positivos / Imunidade nas Mucosas / Genitália Feminina Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2011 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Linfócitos T CD4-Positivos / Imunidade nas Mucosas / Genitália Feminina Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2011 Tipo de documento: Article