Specific migratory dendritic cells rapidly transport antigen from the airways to the thoracic lymph nodes

Antigen transport from the airway mucosa to the thoracic lymph nodes (TLNs) was studied in vivo by intratracheal instillation of fluorescein isothiocy anate (FITC)-conjugated macromolecules. After instillation. FITC+ cells wit h stellate morphology were found deep in the TLN T cell area. Using flow cy tometry, an FITC signal was exclusively detected in CD11c(med-hi)/major his tocompatibility complex class II (MHCII)(hi) cells, representing migratory airway-derived lymph node dendritic cells (AW-LNDCs). No FITC signal accumu lated in lymphocytes and in a CD11c(hi)MHCII(me)d DC group containing a CD8 alpha (hi) subset (non-airway-derived [NAW]-LNDCs). Sorted AW-LNDCs showed long MHCIIbright cytoplasmic processes and intracytoplasmatic FITC+ granul es. The fraction of FITC+ AW-LNDCs peaked after 24 h and had reached baseli ne by day 7. AW-LNDCs were depleted by 7 d of ganciclovir treatment in thym idine kinase transgenic mice, resulting in a strong reduction of FITC-macro molecule transport into the TLNs. Compared with intrapulmonary DCs, AW-LNDC s had a mature phenotype and upregulated levels of MHCII, B7-2, CD40, and i ntracellular adhesion molecule (ICAM)-1. In addition, sorted AW-LNDCs from FITC-ovalbumin (OVA)-instilled animals strongly presented OVA to OVA-TCR tr ansgenic 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.