The locomotion of T lymphocytes within 3-D extracellular matrix (ECM) is a highly dynamic and flexible process following the principles of ameboid movement. Ameboid motility is characterized by a polarized yet simple cell shape allowing high speed, rapid directional oscillations, and low affinity interactions to the substrate that are coupled to a low degree of cytoskeletal organization lacking discrete focal contacts. At the onset of T cell migration, a default program, here described as migration-associated polarization, is initiated, resulting in the polar redistribution of cell surface receptors and cytoskeletal elements. Polarization involves protein cycling either to the leading edge (i.e. LFA-1, CD45RO, chemokine receptors, focal adhesion kinase), to a central polarizing compartment (MTOC, PKC, MARCKS), or into the uropod (CD44, CD43, ICAM-and -3, 1 integrins). The function of such compartment formation may be important in chemotactic response, scanning of encountered cells, and a flexible and adaptive interaction with the ECM itself. Due to the simple shape and a diffusely organized cytoskeleton, the interactions to the surrounding extracellular matrix are rapid and reversible and appear to allow a broad spectrum of molecular migration strategies. These range from (1) adhesive and haptokinetic following i.e. chemokine-induced motility across 2-D surfaces to (2) largely integrin-independent migration predominantly guided by shape change and morphological flexibility, as seen in 3-D type I collagen matrices. Their prominent capacity to rapidly adapt to a given structural environment coupled to contact guidance mechanisms set T cell locomotion apart from slow, focal contact-dependent and more adhesive migration strategies established by fibroblast-like cells and cell clusters. It is therefore likely that, within the tissues, besides chemotactic or haptotactic gradients, the preformed matrix structure has an important impact on T cell trafficking and positioning in health and disease.
INTRODUCTIONThe extracellular matrix provides a structural framework for leukocyte migration and localization. Following transendothelial migration, the interaction of T lymphocytes with the tissue matrix and the migration and positioning therein determine the site and the efficiency of specific immune reactions in both lymphatic as well as peripheral tissues (reviewed in: Shimizu and Shaw, 1991;Ratner, 1992;Friedl and Br6cker, 2000). In this review, the cell biology of T cell migration within the extracellular matrix is summarized with reference to T cell polarization and scanning function favoring both interaction with matrix fibers and recognition of other cells.
SPACIAL ORGANIZATION OF THE EXTRACELLULAR MATRIXIn the body, leukocyte migration is initiated by attachment to and crawling across endothelium (Springer, 1994). It is assumed that, upon transendothelial migration, activation of cell surface receptors and engagement of the c,ytoskeleton are sufficient to trigger long-lasting T cell motility within the tissue (Masuy...