Specific Migratory Dendritic Cells Rapidly Transport Antigen from the Airways to the Thoracic Lymph Nodes
By K. Vermaelen, Ines Carro-Muino, B. Lambrecht, R. Pauwels. Journal of Experimental Medicine, 2001
621 citations recorded by the source corpus.
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 CD11cmed-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 CD11chiMHCIImed DC group containing a CD8αhi subset (non–airway-derived [NAW]-LNDCs). Sorted AW-LNDCs showed long MHCIIbright 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.
Subfields: Immunology
View Paper: https://www.semanticscholar.org/paper/3a89bf6258d63751a463e6e8910b390ed58694df
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In Immunology
- R. Steinman
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- Michel C. Nussenzweig
- I. Mellman
- Steffen Jung
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- M. Aurrand-Lions
Citations in the corpus
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- Dendritic cells: specialized and regulated antigen processing machines. (2001, background): “These In tandem, surface costimulatory molecules (CD80, CD86), include environmental proteins chronically found in the re- MHC class I, and T cell adhesion molecules (e.g., CD48 spiratory and digestive tracts (Vermaelen et al., 2001), as and CD58) are all upregulated.”
- In vivo depletion of lung CD11c+ dendritic cells during allergen challenge abrogates the characteristic features of asthma (2005, background): “We cannot explain at present by what mechanism the CD11c DCs were depleted from the MLNs, but we speculate that they were reduced because of the loss of import of freshly migrating DCs from the mucosa, as these DCs have a very short half-life in the mucosa and continuously migrate to the nodes even ”
- House dust mite allergen induces asthma via TLR4 triggering of airway structural cells (2009, background): “Airway DCs continuously sample inhaled air for the presence of noxious substances via cellular processes that extend across the airway mucosal barrie”
- Inflammatory dendritic cells—not basophils—are necessary and sufficient for induction of Th2 immunity to inhaled house dust mite allergen (2010, background): “…to CD11chi cells (Perrigoue et al., 2009; Sokol et al., 2009), because MHCII expression is not fully restored on migratory DCs (Allenspach et al., 2008), as this might bias our readout of antigen presentation that is strictly dependent on migratory DCs of the lung (Vermaelen et al., 2001).”
- Immunological mechanisms of allergen-specific immunotherapy (2006, background): “These DCs are distributed in an interdigitating network throughout the airways, capturing allergens and migrating to the T-cell area of the mediastinal lymph nodes within 12 hours of exposure to allerge”
- Dendritic Cells Induce Peripheral T Cell Unresponsiveness under Steady State Conditions in Vivo (2001, background): “internalizing potential self-antigens from tissues (47) and from noninfectious environmental proteins (48).”
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- Essential Role of Lung Plasmacytoid Dendritic Cells in Preventing Asthmatic Reactions to Harmless Inhaled Antigen (2004, methodology): “To obtain single lung cell suspensions, lungs were perfused with 20 ml PBS through the right ventricle, minced using iridectomy scissors, and digested with collagenase III and DNase I, as described previously ( 11 ).”