Dual role of dendritic cells in the induction and down-regulation of antigen-specific cutaneous inflammation.
We have previously reported that contact sensitivity (CS) to dinitrofluorobenzene (DNFB) in C57BL/6 mice was mediated by MHC class I-restricted CD8+ T cells and down-regulated by MHC class II-restricted CD4+ T cells. In this study, we analyzed the contribution of dendritic cells (DC) in the induction of these two T cell subsets endowed with opposite functions. Hapten-pulsed skin- and bone marrow-derived DC, obtained from either normal C57BL/6 mice or from MHC class II (I+ II-) and MHC class I (I- II+)-deficient mice, were tested for their ability to prime normal mice for CS to dinitrofluorobenzene. Expression of MHC class I molecules by transferred DC was mandatory both for the induction of CS and for the generation of hapten-specific CD8+ T cells in lymphoid organs. I+ II- DC were as potent as I+ II+ DC in priming for CS, demonstrating that activation of effector CD8+ T cells can occur independently of CD4+ T cell help. I- II+ DC could not immunize for CS, although they could sensitize for a delayed-type hypersensitivity reaction to protein Ags. Moreover, I- II+ DC injected simultaneously with cutaneous sensitization down-regulated the inflammatory response, suggesting that hapten presentation by MHC class II molecules could prime regulatory CD4+ T cells. These results indicate that DC can present haptenated peptides by both MHC class I and class II molecules and activate Ag-specific CD8+ effector and CD4+ regulatory T cell subsets, concurrently and independently.
Krasteva
M
M
INSERM Unite 80, Université Claude Bernard Lyon 1, Faculté Lyon Laennec, France.
Kehren
J
J
Horand
F
F
Akiba
H
H
Choquet
G
G
Ducluzeau
M T
MT
Tédone
R
R
Garrigue
J L
JL
Kaiserlian
D
D
Nicolas
J F
JF
D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology; D016026:Bone Marrow Transplantation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D003877:Dermatitis, Contact / Q000209:etiology* / Q000276:immunology*; D004139:Dinitrofluorobenzene / Q000276:immunology; D015536:Down-Regulation / Q000276:immunology*; D000078404:Epidermal Cells; D004817:Epidermis / Q000276:immunology; D000939:Epitopes / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology; D007108:Immune Tolerance / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D004139:Dinitrofluorobenzene