title: Specific migratory dendritic cells rapidly transport antigen from the airways to the thoracic lymph nodes.
abstract: Antigen transport from the airway mucosa to the thoracic lymph nodes (TLNs) was studied in vivo by intratracheal instillation of fluorescein isothiocyanate (FITC)-conjugated macromolecules. After instillation, FITC(+) cells with stellate morphology were found deep in the TLN T cell area. Using flow cytometry, an FITC signal was exclusively detected in CD11c(med-hi)/major histocompatibility complex class II (MHCII)(hi) cells, representing migratory airway-derived lymph node dendritic cells (AW-LNDCs). No FITC signal accumulated in lymphocytes and in a CD11c(hi)MHCII(med) DC group containing a CD8 alpha(hi) subset (non-airway-derived [NAW]-LNDCs). Sorted AW-LNDCs showed long MHCII(bright) cytoplasmic processes and intracytoplasmatic FITC(+) granules. The fraction of FITC(+) AW-LNDCs peaked after 24 h and had reached baseline by day 7. AW-LNDCs were depleted by 7 d of ganciclovir treatment in thymidine kinase transgenic mice, resulting in a strong reduction of FITC-macromolecule transport into the TLNs. Compared with intrapulmonary DCs, AW-LNDCs had a mature phenotype and upregulated levels of MHCII, B7-2, CD40, and intracellular adhesion molecule (ICAM)-1. In addition, sorted AW-LNDCs from FITC-ovalbumin (OVA)-instilled animals strongly presented OVA to OVA-TCR transgenic T cells. These results validate the unique sentinel role of airway DCs, picking up antigen in the airways and delivering it in an immunogenic form to the T cells in the TLNs.
authors.affiliation: Department of Respiratory Diseases, Ghent University Hospital, Ghent B-9000, Belgium. karim.vermaelen@rug.ac.be
authors.forename: K Y
authors.initials: KY
authors.lastname: Vermaelen
authors.forename: I
authors.initials: I
authors.lastname: Carro-Muino
authors.forename: B N
authors.initials: BN
authors.lastname: Lambrecht
authors.forename: R A
authors.initials: RA
authors.lastname: Pauwels
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D001693:Biological Transport, Active; D002465:Cell Movement; D003713:Dendritic Cells / Q000276:immunology* / Q000502:physiology; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D016130:Immunophenotyping; D008168:Lung / Q000166:cytology* / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology* / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology
chemical_list: D005456:Fluorescent Dyes; D010047:Ovalbumin; D016650:Fluorescein-5-isothiocyanate