A role for LFA‐1 in delaying T‐lymphocyte egress from lymph nodes
A role for LFA‐1 in delaying T‐lymphocyte egress from lymph nodes
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.
- University of Duisburg-Essen Germany
- Essen University Hospital Germany
- London Research Institute United Kingdom
- Otto-von-Guericke University Magdeburg Germany
Male, Mice, Knockout, Time Factors, Chemokine CCL21, T-Lymphocytes, Medizin, Membrane Transport Proteins, Intercellular Adhesion Molecule-1, Lymphocyte Function-Associated Antigen-1, Mice, Inbred C57BL, Chemotaxis, Leukocyte, Mice, Sphingosine, Animals, Female, Lymph Nodes, Lysophospholipids, Cells, Cultured, Glycoproteins
Male, Mice, Knockout, Time Factors, Chemokine CCL21, T-Lymphocytes, Medizin, Membrane Transport Proteins, Intercellular Adhesion Molecule-1, Lymphocyte Function-Associated Antigen-1, Mice, Inbred C57BL, Chemotaxis, Leukocyte, Mice, Sphingosine, Animals, Female, Lymph Nodes, Lysophospholipids, Cells, Cultured, Glycoproteins
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