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J Immunol. 2013 Aug 1;191(3):1188-99. doi: 10.4049/jimmunol.1300739. Epub 2013 Jul 1.

Dendritic cells regulate high-speed interstitial T cell migration in the lymph node via LFA-1/ICAM-1.

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Department of Molecular Genetics, Institute of Biomedical Science, Kansai Medical University, Core Research for Evolutionary Science and Technology, Japan Science and Technology Agency, Hirakata, Osaka 573-1010, Japan.


T lymphocytes vigorously migrate within the paracortex of lymph nodes (LNs) in search of cognate Ags that are presented by dendritic cells (DCs). However, the mechanisms that support T cells to exert the highest motility in a densely packed LN microenvironment are not fully understood. Two-photon microscopy using LN tissue slices revealed that LFA-1 and ICAM-1 were required for high-velocity migration (>10 μm/min) with relatively straight movement. Importantly, ICAM-1 expressed by myeloid lineages, most likely DCs, but not stromal cells or lymphocytes, was sufficient to support the high-velocity migration. Visualizing DCs in the LN from CD11c-EYFP mice showed that T cells traveled over thin dendrites and the body of DCs. Interestingly, DCs supported T cell motility in vitro in chemokine- and ICAM-1-dependent manners. Moreover, an acute lymphopenic environment in the LN significantly increased LFA-1 dependency for T cell migration, indicating that lymphocyte density modulates the use of LFA-1. Therefore, our results indicate that LFA-1/ICAM-1-dependent interactions between T cells and DCs play a crucial role not only in supporting firm arrest during Ag recognition but also in facilitating the Ag scanning processes.

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