CD103- and CD103+ bronchial lymph node dendritic cells are specialized in presenting and cross-presenting innocuous antigen to CD4+ and CD8+ T cells.
Dendritic cells (DC) are able to capture, process, and present exogenous Ag to CD8(+) T lymphocytes through MHC class I, a process referred to as cross-presentation. In this study, we demonstrate that CD103(+) (CD11c(high)CD11b(low)) and CD103(-) (CD11c(int)CD11b(high)) DC residing in the lung-draining bronchial lymph node (brLN) have evolved to acquire opposing functions in presenting innocuous inhaled Ag. Thus, under tolerogenic conditions, CD103(-) DC are specialized in presenting innocuous Ag to CD4(+) T cells, whereas CD103(+) DC, which do not express CD8alpha, are specialized in presenting Ag exclusively to CD8(+) T cells. In CCR7-deficient but not in plt/plt mice, Ag-carrying CD103(+) DC are largely absent in the brLN, although CD103(+) DC are present in the lung of CCR7-deficient mice. As a consequence, adoptively transferred CD8(+) T cells can be activated under tolerizing conditions in plt/plt but not in CCR7-deficient mice. These data reveal that CD103(+) brLN DC are specialized in cross-presenting innocuous inhaled Ag in vivo. Because these cells are largely absent in CCR7(-/-) mice, our findings strongly suggest that brLN CD103(+) DC are lung-derived and that expression of CCR7 is required for their migration from the lung into its draining lymph node.
del Rio
Maria-Luisa
ML
Institute of Immunology, Hannover Medical School, Hannover, Germany.
Rodriguez-Barbosa
Jose-Ignacio
JI
Kremmer
Elisabeth
E
Förster
Reinhold
R
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology*; D015703:Antigens, CD / Q000096:biosynthesis / Q000378:metabolism*; D001980:Bronchi / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D045142:Cross-Priming / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004527:Egg Proteins / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D016130:Immunophenotyping; D039001:Integrin alpha Chains / Q000096:biosynthesis / Q000378:metabolism*; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics
D015703:Antigens, CD; C515371:Ccr7 protein, mouse; D004527:Egg Proteins; D039001:Integrin alpha Chains; C111390:OVA 323-339; C110366:OVA-8; D010446:Peptide Fragments; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; C091367:alpha E integrins; D010047:Ovalbumin