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CD4(+) T-cell immunity in the female genital tract is critically dependent on local mucosal immunization.

Artikel i vetenskaplig tidskrift
Författare Ellen Marks
Anja Helgeby
Jan O Andersson
Karin Schön
Nils Y Lycke
Publicerad i European journal of immunology
Volym 41
Nummer/häfte 9
Sidor 2642-53
ISSN 1521-4141
Publiceringsår 2011
Publicerad vid Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi
Sidor 2642-53
Språk en
Länkar dx.doi.org/10.1002/eji.201041297
Ämnesord Administration, Intravaginal, Adoptive Transfer, Animals, Antigens, immunology, CD4-Positive T-Lymphocytes, drug effects, immunology, metabolism, pathology, Cell Proliferation, drug effects, Cells, Cultured, Cholera Toxin, administration & dosage, Estradiol, administration & dosage, Female, Genitalia, Female, pathology, Humans, Immunity, Mucosal, drug effects, genetics, Immunization, Secondary, Lymphocyte Activation, drug effects, genetics, Mice, Mice, Inbred BALB C, Mice, Transgenic, Ovalbumin, administration & dosage, immunology, Progesterone, administration & dosage
Ämneskategorier Immunologi inom det medicinska området

Sammanfattning

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.

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