Abstract
Although much is known about the migration of T cells from blood to lymph nodes, less is known about the mechanisms regulating the migration of T cells from tissues into lymph nodes through afferent lymphatics. Here we investigated T cell egress from nonlymphoid tissues into afferent lymph in vivo and developed an experimental model to recapitulate this process in vitro. Agonism of sphingosine 1-phosphate receptor 1 inhibited the entry of tissue T cells into afferent lymphatics in homeostatic and inflammatory conditions and caused the arrest, mediated at least partially by interactions of the integrin LFA-1 with its ligand ICAM-1 and of the integrin VLA-4 with its ligand VCAM-1, of polarized T cells at the basal surface of lymphatic but not blood vessel endothelium. Thus, the increased sphingosine 1-phosphate present in inflamed peripheral tissues may induce T cell retention and suppress T cell egress.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Movement
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Endothelium, Lymphatic / immunology
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Fingolimod Hydrochloride
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Homeostasis
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Inflammation / immunology
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Integrin alpha4beta1 / immunology
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Intercellular Adhesion Molecule-1 / immunology
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Lymph Nodes / immunology
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Lymphatic Vessels / immunology*
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Lymphocyte Function-Associated Antigen-1 / immunology
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Lysophospholipids / metabolism*
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Mice
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Mice, Inbred C57BL
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Models, Immunological*
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Propylene Glycols / pharmacology
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Receptors, Lysosphingolipid / agonists
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Receptors, Lysosphingolipid / antagonists & inhibitors
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Receptors, Lysosphingolipid / immunology*
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Signal Transduction
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Sphingosine / analogs & derivatives*
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Sphingosine / metabolism
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Sphingosine / pharmacology
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T-Lymphocytes / immunology*
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Vascular Cell Adhesion Molecule-1 / immunology
Substances
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Integrin alpha4beta1
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Lymphocyte Function-Associated Antigen-1
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Lysophospholipids
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Propylene Glycols
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Receptors, Lysosphingolipid
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Vascular Cell Adhesion Molecule-1
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Intercellular Adhesion Molecule-1
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sphingosine 1-phosphate
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Fingolimod Hydrochloride
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Sphingosine