The murine buccal mucosa is an inductive site for priming class I-restricted CD8+ effector T cellsin vivo

Abstract

The present study shows that Langerhans cells of the buccal mucosa and the skin share a similar phenotype, including in situ expression of MHC class II, the mannose receptor DEC-205 and CD11c, and absence of the costimulatory molecules B7.1, B7.2 and CD40 as well as Fas. Application of 2,4-dinitrofluorobenzene (DNFB) onto the buccal mucosa is associated with a rapid migration of dendritic cells (DC) to the epithelium and induction of B7.2 expression on some DC. Buccal sensitization with DNFB elicited a specific contact sensitivity (CS) in response to skin challenge, mediated by class I-restricted CD8+ effector T cells and down-regulated by class II-restricted CD4+ T cells, demonstrated by the lack of priming of class I-deficient mice and the enhanced response of class II-deficient mice, respectively. CS induced by buccal immunization is associated with priming of class I-restricted CD8+ effector T cells endowed with hapten-specific cytotoxic activity. Thus, the buccal epithelium is an inductive site, equivalent to the epidermis, for the generation of CS independent of CD4 help, and of cytotoxic T lymphocyte (CTL) responses mediated by class I-restricted CD8+ T cells. We propose that immunization through the buccal mucosa, which allows antigen presentation by epithelial DC efficient for priming systemic class I-restricted CD8+ CTL, may be a valuable approach for single-dose mucosal vaccination with subunit vaccines.

Oral Administration of Hapten Inhibits In Vivo Induction of Specific Cytotoxic CD8+ T Cells Mediating Tissue Inflammation: A Role for Regulatory CD4+ T Cells

“…Spleens recovered from DNFB-fed or vehicle-fed mice on day 5 after epicutaneous DNFB sensitization were tested for hapten-specific CTL activity as previously described (22). Briefly, spleen cells were restimulated in vitro with mitomycin C-treated DNBS-derivatized syngeneic spleen cells, at a 1:1 ratio.…”

“…Specific binding was revealed with a streptavidin-peroxidase kit (DAKO, Glostrup, Denmark) and AEC in the presence of H 2 O 2 as substrate as described (22). Sections were counterstained with hematoxylin.…”

CCR7-CCL19/CCL21-Regulated Dendritic Cells Are Responsible for Effectiveness of Sublingual Vaccination

“…Buccal mucosa, an oral mucosa, has received attention for induction of T cell responses, especially class I-restricted CD8 ϩ effector cells in mice (11). CD8 ϩ T cell cross-priming was induced by painting the buccal mucosa with the contact sensitizer 2,4-dinitro-1-fluorobenzene, leading to rapid recruitment of dendritic cells (DCs) into epithelium which is completely dependent on MIP-3␣/CCL20 interaction (12).…”

Cellules dendritiques des muqueuses et de la peau

“…Plusieurs groupes ont observé que l'exposition des muqueuses et/ou de la peau à des virus, des bactéries [22], des adjuvants tels que la toxine cholérique et la flagelline [23,24], à la nucléoprotéine du virus de la rougeole (NP) [25,26], ou à des produits chimiques à pouvoir sensibilisant [26,27], provoquait une accumulation de DC au site d'immunisation. Le fait que la plupart de ces Ag soient de puissants immunogènes capables d'activer des CTL CD8 + spécifiques in vivo en l'absence de LT CD4 + a permis de postuler que leur immunogénicité pouvait être dépendante de DC néo-recrutées.…”