title: T Cell Migration from Inflamed Skin to Draining Lymph Nodes Requires Intralymphatic Crawling Supported by ICAM-1/LFA-1 Interactions.
abstract: T cells are the most abundant cell type found in afferent lymph, but their migration through lymphatic vessels (LVs) remains poorly understood. Performing intravital microscopy in the murine skin, we imaged T cell migration through afferent LVs in vivo. T cells entered into and actively migrated within lymphatic capillaries but were passively transported in contractile collecting vessels. Intralymphatic T cell number and motility were increased during contact-hypersensitivity-induced inflammation and dependent on ICAM-1/LFA-1 interactions. In vitro, blockade of endothelial cell-expressed ICAM-1 reduced T cell adhesion, crawling, and transmigration across lymphatic endothelium and decreased T cell advancement from capillaries into lymphatic collectors in skin explants. In vivo, T cell migration to draining lymph nodes was significantly reduced upon ICAM-1 or LFA-1 blockade. Our findings indicate that T cell migration through LVs occurs in distinct steps and reveal a key role for ICAM-1/LFA-1 interactions in this process.
authors.affiliation: Institute of Pharmaceutical Sciences, ETH Zurich, 8093 Zurich, Switzerland; Department of Immunology and Immunotherapy, Center for Applied Medical Research, 31009 Pamplona, Spain.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Teijeira
authors.affiliation: Institute of Pharmaceutical Sciences, ETH Zurich, 8093 Zurich, Switzerland.
authors.forename: Morgan C
authors.initials: MC
authors.lastname: Hunter
authors.affiliation: Institute of Pharmaceutical Sciences, ETH Zurich, 8093 Zurich, Switzerland.
authors.forename: Erica
authors.initials: E
authors.lastname: Russo
authors.affiliation: Institute of Pharmaceutical Sciences, ETH Zurich, 8093 Zurich, Switzerland.
authors.forename: Steven T
authors.initials: ST
authors.lastname: Proulx
authors.affiliation: Institute of Pharmaceutical Sciences, ETH Zurich, 8093 Zurich, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Frei
authors.affiliation: School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Gudrun F
authors.initials: GF
authors.lastname: Debes
authors.affiliation: University of York, YO10 5DD York, UK.
authors.forename: Marc
authors.initials: M
authors.lastname: Coles
authors.affiliation: Department of Immunology and Immunotherapy, Center for Applied Medical Research, 31009 Pamplona, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Melero
authors.affiliation: Institute of Pharmaceutical Sciences, ETH Zurich, 8093 Zurich, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Detmar
authors.affiliation: Department of Immunology and Immunotherapy, Center for Applied Medical Research, 31009 Pamplona, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Rouzaut
authors.affiliation: Institute of Pharmaceutical Sciences, ETH Zurich, 8093 Zurich, Switzerland. Electronic address: cornelia.halin@pharma.ethz.ch.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Halin
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000502:physiology; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D005434:Flow Cytometry; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000737:chemistry / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology / Q000502:physiology; D008198:Lymph Nodes / Q000378:metabolism*; D042601:Lymphatic Vessels / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1 / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D010081:Oxazolone / Q000633:toxicity; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D059008:Time-Lapse Imaging; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D016169:Lymphocyte Function-Associated Antigen-1; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D010081:Oxazolone; D007371:Interferon-gamma
keywords: ICAM-1; T cell; cell migration; inflammation; intravital microscopy; lymphatic vessels