Dendritic cells rapidly recruited into epithelial tissues via CCR6/CCL20 are responsible for CD8+ T cell crosspriming in vivo.
The nature of dendritic cell(s) (DC[s]) that conditions efficient in vivo priming of CD8+ CTL after immunization via epithelial tissues remains largely unknown. Here, we show that myeloid DCs rapidly recruited by adjuvants into the buccal mucosa or skin are essential for CD8+ T cell crosspriming. Recruitment of circulating DC precursors, including Gr1+ monocytes, precedes the sequential accumulation of CD11c+ MHC class II+ DCs in dermis and epithelium via a CCR6/CCL20-dependent mechanism. Remarkably, a defect in CCR6, local neutralization of CCL20, or depletion of monocytes prevents in vivo priming of CD8+ CTL against an innocuous protein antigen administered with adjuvant. In addition, transfer of CCR6-sufficient Gr1+ monocytes restores CD8+ T cell priming in CCR6( degrees / degrees ) mice via a direct Ag presentation mechanism. Thus, newly recruited DCs likely derived from circulating monocytes are responsible for efficient crosspriming of CD8+ CTL after mucosal or skin immunization.
INSERM U404 "Immunité et Vaccination", IFR128 BioSciences Lyon-Gerland, F-69365 Lyon, France.
Marie
M
Le Borgne
Nathalie
N
Etchart
Anne
A
Goubier
Sergio A
SA
Lira
Jean Claude
JC
Sirard
Nico
N
van Rooijen
Christophe
C
Caux
Smina
S
Aït-Yahia
Alain
A
Vicari
Dominique
D
Kaiserlian
Bertrand
B
Dubois
D000276:Adjuvants, Immunologic; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002465:Cell Movement; D054418:Chemokine CCL20; D019742:Chemokines, CC / Q000378:metabolism / Q000502:physiology*; D004002:Clodronic Acid / Q000494:pharmacology; D003713:Dendritic Cells / Q000276:immunology*; D020405:Dermis / Q000378:metabolism; D004139:Dinitrofluorobenzene / Q000494:pharmacology; D004848:Epithelium / Q000276:immunology / Q000378:metabolism; D005260:Female; D006183:H-2 Antigens / Q000235:genetics / Q000502:physiology; D007114:Immunization; D007801:Langerhans Cells / Q000502:physiology; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009061:Mouth Mucosa / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D009698:Nucleoproteins / Q000276:immunology; D054399:Receptors, CCR6; D019707:Receptors, Chemokine / Q000235:genetics / Q000502:physiology*; D013234:Stem Cells / Q000502:physiology
D000276:Adjuvants, Immunologic; C108355:CCL20 protein, human; C106311:CCR6 protein, human; D054418:Chemokine CCL20; D019742:Chemokines, CC; D006183:H-2 Antigens; D019402:Macrophage Inflammatory Proteins; D009698:Nucleoproteins; D054399:Receptors, CCR6; D019707:Receptors, Chemokine; D004002:Clodronic Acid; D004139:Dinitrofluorobenzene