Abstract
T cells are highly concentrated in the lymph node (LN) paracortex, which serves an important role in triggering adoptive immune responses. Live imaging using two-photon laser scanning microscopy revealed vigorous and non-directional T cell migration within this area at average velocity of more than 10 μm/min. Active interstitial T cell movement is considered to be crucial for scanning large numbers of dendritic cells (DCs) to find rare cognate antigens. However, the mechanism by which T cells achieve such high-speed movement in a densely packed, dynamic tissue environment is not fully understood. Several new findings suggest that fibroblastic reticular cells (FRCs) and DCs control T cell movement in a multilateral manner. Chemokines and lysophosphatidic acid produced by FRCs cooperatively promote the migration, while DCs facilitate LFA-1-dependent motility via expression of ICAM-1. Furthermore, the highly dense and confined microenvironment likely plays a key role in anchorage-independent motility. We propose that T cells dynamically switch between two motility modes; anchorage-dependent and -independent manners. Unique tissue microenvironment and characteristic migration modality of T cells cooperatively generate high-speed interstitial movement in the LN.
Highlights
In addition to their strategic locations throughout the lymphatic vascular system, lymph nodes (LN) contain a variety of immune cells, lymphocytes, which make them an ideal device for coupling lymph fluid filtration to the collection of antigens and induction of adaptive immune responses [1, 2]
Chemokine signaling controls actomyosin machinery that mediates both directional movements along a gradient and non-directional migration under uniform concentrations that is reminiscent of T cell migration in LNs
LFA-1 blockage dramatically inhibits migration but not polarization, indicating that adhesion mediated by LFA-1 to stromal ICAM-1 is required for T cell movement in this setting. (B) Various treatments affect T cell migration on a LN stromal monolayer [partially adapted and modified from Ref. [27]]
Summary
In addition to their strategic locations throughout the lymphatic vascular system, lymph nodes (LN) contain a variety of immune cells, lymphocytes, which make them an ideal device for coupling lymph fluid filtration to the collection of antigens and induction of adaptive immune responses [1, 2]. Chemokine signaling controls actomyosin machinery that mediates both directional movements along a gradient (chemotaxis) and non-directional migration under uniform concentrations (chemokinesis) that is reminiscent of T cell migration in LNs. the inhibition of Gαi-coupled receptors by pertussis toxin markedly reduced INTM by 40–50% in velocity [35, 36]. LFA-1 blockage dramatically inhibits migration but not polarization, indicating that adhesion mediated by LFA-1 to stromal ICAM-1 is required for T cell movement in this setting.
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