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Node via LFA-1/ICAM-1 Interstitial T Cell Migration in the Lymph Dendritic Cells Regulate High-Speed

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 micro-environment 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 m m/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. The Journal of Immunology , 2013, 191: 000–000.