The murine buccal mucosa is an inductive site for priming class I-restricted CD8+ effector T cells in vivo.
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.
Desvignes
C
C
INSERM U404 Immunité et Vaccination, Lyon, France.
Estèves
F
F
Etchart
N
N
Bella
C
C
Czerkinsky
C
C
Kaiserlian
D
D
D000818:Animals; D018122:B7-1 Antigen / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002610:Cheek; D003713:Dendritic Cells / Q000502:physiology; D003877:Dermatitis, Contact / Q000209:etiology; D004139:Dinitrofluorobenzene; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000502:physiology*; D007114:Immunization; D007801:Langerhans Cells / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009061:Mouth Mucosa / Q000276:immunology*; D051381:Rats
D018122:B7-1 Antigen; D015395:Histocompatibility Antigens Class I; D004139:Dinitrofluorobenzene