Langerhans cells prime IL-17-producing T cells and dampen genital cytotoxic responses following mucosal immunization.
Langerhans cells (LCs) are dendritic cells (DCs) localized in stratified epithelia, such as those overlaying skin, buccal mucosa, and vagina. The contribution of LCs to the promotion or control of immunity initiated at epithelial sites remains debated. We report in this paper that an immunogen comprising OVA linked to the B subunit of cholera toxin, used as delivery vector, was efficient to generate CTLs after vaginal immunization. Using Lang-EGFP mice, we evaluated the contribution of distinct DC subsets to the generation of CD4 and CD8 T cell responses. We demonstrate that the vaginal epithelium, unlike the skin epidermis, includes a minor population of LCs and a major subset of langerin(-) DCs. Intravaginally administered Ag is taken up by LCs and langerin(-) DCs and carried up to draining lymph nodes, where both subsets prime CD8 T cells, unlike blood-derived DCs, although with distinct capabilities. LCs prime CD8 T cells with a cytokine profile dominated by IL-17, whereas Lang(-) DCs induce IFN-gamma-producing T cells. Using Lang-DTR-EGFP mice to ensure a transient ablation of LCs, we found that these cells not only are dispensable for the generation of genital CTL responses but also downregulate these responses, by a mechanism that may involve IL-10 and IL-17 cytokines. This finding has implications for the development of mucosal vaccines and immunotherapeutic strategies designed for the targeting of DCs.
Hervouet
Catherine
C
Institut National de la Santé et de la Recherche Médicale U634, Faculté de Médecine Pasteur, France.
Luci
Carmelo
C
Rol
Nicolas
N
Rousseau
Déborah
D
Kissenpfennig
Adrien
A
Malissen
Bernard
B
Czerkinsky
Cecil
C
Anjuère
Fabienne
F
D000282:Administration, Intravaginal; D000595:Amino Acid Sequence; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000008:administration & dosage / Q000276:immunology; D018920:Coculture Techniques; D003601:Cytotoxicity Tests, Immunologic / Q000379:methods; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005260:Female; D020381:Interleukin-17 / Q000096:biosynthesis*; D007801:Langerhans Cells / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009061:Mouth Mucosa / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000276:immunology*; D014621:Vagina / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D020381:Interleukin-17; C111390:OVA 323-339; D010446:Peptide Fragments; D018074:Vaccines, Conjugate; D010047:Ovalbumin; D002772:Cholera Toxin