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

Publication date: 24 January 2017
Source:Cell Reports, Volume 18, Issue 4
Author(s): 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
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.

Graphical abstract

Teaser

T cell migration through afferent lymphatic vessels contributes to immune surveillance, but the cellular mechanisms of this process are largely unknown. Using intravital microscopy, Teijeira et al. show that T cells crawl in an ICAM-1/LFA-1-dependent manner within inflamed dermal lymphatic capillaries but only flow with lymph once in contracting collectors.


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