T Cell Migration from Inflamed Skin to Draining Lymph Nodes Requires Intralymphatic Crawling Supported by ICAM-1/LFA-1 Interactions

Alvaro Teijeira; Morgan C Hunter; Erica Russo; Steven T Proulx; Thomas Frei; Gudrun F Debes; Marc Coles; Ignacio Melero; Michael Detmar; Ana Rouzaut; Cornelia Halin

doi:10.1016/j.celrep.2016.12.078

T Cell Migration from Inflamed Skin to Draining Lymph Nodes Requires Intralymphatic Crawling Supported by ICAM-1/LFA-1 Interactions

Cell Rep. 2017 Jan 24;18(4):857-865. doi: 10.1016/j.celrep.2016.12.078.

Authors

Affiliations

¹ Institute of Pharmaceutical Sciences, ETH Zurich, 8093 Zurich, Switzerland; Department of Immunology and Immunotherapy, Center for Applied Medical Research, 31009 Pamplona, Spain.
² Institute of Pharmaceutical Sciences, ETH Zurich, 8093 Zurich, Switzerland.
³ School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
⁴ University of York, YO10 5DD York, UK.
⁵ Department of Immunology and Immunotherapy, Center for Applied Medical Research, 31009 Pamplona, Spain.
⁶ Institute of Pharmaceutical Sciences, ETH Zurich, 8093 Zurich, Switzerland. Electronic address: [email protected].

PMID: 28122237
DOI: 10.1016/j.celrep.2016.12.078

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.

Keywords: ICAM-1; T cell; cell migration; inflammation; intravital microscopy; lymphatic vessels.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
CD4-Positive T-Lymphocytes / cytology
CD4-Positive T-Lymphocytes / immunology
CD4-Positive T-Lymphocytes / physiology
CD8-Positive T-Lymphocytes / cytology
CD8-Positive T-Lymphocytes / immunology
CD8-Positive T-Lymphocytes / physiology
Cell Adhesion / drug effects
Cell Movement / drug effects
Flow Cytometry
Inflammation / chemically induced
Inflammation / immunology*
Inflammation / pathology
Intercellular Adhesion Molecule-1 / chemistry
Intercellular Adhesion Molecule-1 / metabolism*
Interferon-gamma / pharmacology
Killer Cells, Natural / cytology
Killer Cells, Natural / immunology
Killer Cells, Natural / physiology
Lymph Nodes / metabolism*
Lymphatic Vessels / metabolism
Lymphocyte Function-Associated Antigen-1 / chemistry
Lymphocyte Function-Associated Antigen-1 / metabolism*
Mice
Mice, Inbred C57BL
Mice, Transgenic
Microscopy, Confocal
Oxazolone / toxicity
Skin / metabolism*
Skin / pathology
T-Lymphocytes / cytology
T-Lymphocytes / immunology
T-Lymphocytes / physiology*
Time-Lapse Imaging
Tumor Necrosis Factor-alpha / pharmacology

Substances

Lymphocyte Function-Associated Antigen-1
Tumor Necrosis Factor-alpha
Intercellular Adhesion Molecule-1
Oxazolone
Interferon-gamma