title: A role for LFA-1 in delaying T-lymphocyte egress from lymph nodes.
abstract: Lymphocytes use the integrin leukocyte function-associated antigen-1 (LFA-1) to cross the vasculature into lymph nodes (LNs), but it has been uncertain whether their migration within LN is also LFA-1 dependent. We show that LFA-1 mediates prolonged LN residence as LFA-1(-/-) CD4 T cells have significantly decreased dwell times compared with LFA-1(+/+) T cells, a distinction lost in hosts lacking the major LFA-1 ligand ICAM-1. Intra-vital two-photon microscopy revealed that LFA-1(+/+) and LFA-1(-/-) T cells reacted differently when probing the ICAM-1-expressing lymphatic network. While LFA-1(+/+) T cells returned to the LN parenchyma with greater frequency, LFA-1(-/-) T cells egressed promptly. This difference in exit behaviour was a feature of egress through all assessed lymphatic exit sites. We show that use of LFA-1 as an adhesion receptor amplifies the number of T cells returning to the LN parenchyma that can lead to increased effectiveness of T-cell response to antigen. Thus, we identify a novel function for LFA-1 in guiding T cells at the critical point of LN egress when they either exit or return into the LN for further interactions.
authors: Institute of Molecular and Clinical Immunology, Otto von Guericke University Magdeburg, Magdeburg, Germany.
authors: Peter
authors: P
authors: Reichardt
authors: Irene
authors: I
authors: Patzak
authors: Kristian
authors: K
authors: Jones
authors: Eloho
authors: E
authors: Etemire
authors: Matthias
authors: M
authors: Gunzer
authors: Nancy
authors: N
authors: Hogg
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D054421:Chemokine CCL21 / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000235:genetics*; D005260:Female; D006023:Glycoproteins / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008246:Lysophospholipids / Q000494:pharmacology; D008297:Male; D026901:Membrane Transport Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013110:Sphingosine / Q000031:analogs & derivatives / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D013997:Time Factors
chemical_list: D054421:Chemokine CCL21; D006023:Glycoproteins; D018799:Intercellular Adhesion Molecule-1; D016169:Lymphocyte Function-Associated Antigen-1; D008246:Lysophospholipids; D026901:Membrane Transport Proteins; D013110:Sphingosine; C492273:LYVE1 protein, mouse; C060506:sphingosine 1-phosphate