CD4(-LYMPHOCYTES MIGRATING IN 3-DIMENSIONAL COLLAGEN LATTICES LACK FOCAL ADHESIONS AND UTILIZE BETA-1 INTEGRIN-INDEPENDENT STRATEGIES FOR POLARIZATION, INTERACTION WITH COLLAGEN-FIBERS AND LOCOMOTION() T)

Cell migration may depend on integrin-mediated adhesion to and deadhes ion from extracellular matrix ligands. This concept, however, has not yet been confirmed for T lymphocytes migrating in three-dimensional ex tracellular matrices. We investigated receptor involvement in T cell m igration combining a three-dimensional collagen matrix model with time -lapse videomicroscopy, computer-assisted cell tracking and confocal m icroscopy. In collagen lattices, the migration of CD4(+) T cells (1) i nvolved interactions with collagen fibers at the leading edge and urop od likewise, (2) occurred independently of the co-clustering of beta 1 , beta 2, or beta 3 integrins with F-actin, focal adhesion kinase, and phosphotyrosine at interactions with collagen fibers, (3) was counter acted by high-affinity beta 1 integrin binding induced by antibody TS2 /16; however, (4) the migration could not be blocked by a combination of adhesion-perturbing anti-beta 1, -beta 2, -beta 3, and alpha v inte grin antibodies. Integrin blocking neither affected cell polarization, interaction with fibers, beta 1 integrin distribution, migration velo city, path structure, nor the number of locomoting cells in spontaneou sly migrating or concanavalin A-activated cells. Hence, T lymphocytes migrating in three-dimensional collagen matrices may utilize highly tr ansient interactions with collagen fibers of low adhesivity, thereby d iffering from focal adhesion-dependent migration strategies employed b y other cells.