DIRECT AND RAPID INDUCTION OF MIGRATION IN HUMAN CD4(-LYMPHOCYTES WITHIN 3-DIMENSIONAL COLLAGEN MATRICES MEDIATED BY SIGNALING VIA CD3 AND() T)OR CD2/

Specific activation of T cells requires stable cell-cell interaction; however, little is known how the transition from a previously motile s tate into a sessile state following activation is achieved. We investi gated the direct effect of T-cell receptor (TCR)/CD3 complex engagemen t and/or stimulation of the accessory molecule CD2 on the locomotion o f peripheral human T cells within three-dimensional (3-D) collagen lat tices. Simultaneous engagement of CD3 and CD2 very potently stimulated T-cell migration, resulting in the recruitment of previously sessile cells (about 24% of the total population was additionally recruited) a s well as an increase in the mean duration of active locomotion. This induction of migration was accompanied by an increased tyrosine phosph orylation of a 125000 MW substrate corresponding to the focal adhesion kinase. Using confocal laser scanning microscopy we detected antibody -induced receptor capping into the uropod of migrating T cells whereas untreated control cells displayed an even distribution of CD3 and CD2 on the cell surface. Less pronounced induction of locomotion was achi eved following triggering of CD3 or CD2 alone. Thus, in 3-D collagen l attices specific T-cell activation did not lead to cessation of cellul ar migration but rather induced cytoskeletal activity that ultimately resulted in vigorous locomotory activity.