Journal
EMBO JOURNAL
Volume 32, Issue 6, Pages 829-843Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/emboj.2013.33
Keywords
LFA-1; lymphatics; lymph node; migration; T cells
Categories
Funding
- Cancer Research UK
- German Research Foundation [SFB854, SPP1468]
- C. J. Martin Fellowship
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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(+/+) Tcells, 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. The EMBO Journal (2013) 32, 829-843. doi:10.1038/emboj.2013.33; Published online 26 February 2013
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