For homeostasis, T cells integrate non-cognate TCR-dependent and -independent signals to survive and weakly proliferate. In contrast to antigen-specific, stable, and long-lived contacts, signaling in short-lived homeostatic interactions depends upon the coordination of ongoing T-cell migration on the surface of DC and signaling at the cell-cell junction.To mimic peripheral tissues and analyze how T-cell migration and cell-cell signaling are integrated, we used live-cell imaging and 3-D reconstruction of fixed conjugates between DO11.10 T cells and DC in 3-D low-density collagen matrices. T cells simultaneously maintained amoeboid migration and polarized towards the DC, leading to a fully dynamic interaction plane that delivered signals for homeostatic T-cell survival and proliferation. The contact plane comprised three zones, the actin-rich leading edge poor in signal but driving migration, a mid-zone mediating TCR/MHC-induced signal associated with proliferation, and the rear uropod mediating predominantly MHC-independent signals. Thus a dynamic immunological synapse with distinct signaling sectors enables moving T cells to serially sample resident tissue cells and acquire molecular information ''en passant''.Key words: Immunological synpase . Migration . T-cell homeostasis Supporting Information available online
IntroductionLymphocyte recirculation and amoeboid migration within secondary lymphoid tissues are mandatory for effective immune surveillance. In secondary lymphoid organs, T cells utilize amoeboid migration along fibroblastic reticular cells as guidance cues to rapidly scan APC for cognate antigen [1,2]. Whereas the role of migration in scanning cells for their antigenic repertoire is well established, its role in T-cell activation and signal induction is less clear. On the one hand, in vitro models suggest that the recognition of antigenic peptide leads to migratory arrest [3] and the formation of a concentrically segregated interaction plane with a peripheral ring of adhesion molecules surrounding a central accumulation of TCR, the immunological synapse (IS) [4,5]. Conversely, the most powerful APC, DC, activate T cells via both stably adhesive and migratory contacts, depending on signal strength and phase of T-cell priming [6][7][8][9] and do not induce a segregated IS [10,11]. In a lipid bilayer model, the concept of productive TCR signaling despite T-cell migration is suggested by intermittent episodes of T-cell migration, which are associated with enhanced TCR signaling and IL-2 secretion [12]. Thus, the spectrum of activating T-cell/APC interactions is diverse and T-cell migration appears to contribute to rather than interfere with signal induction. However, as adhesive and migratory contact phases alternate sequentially in most experimental models, the specific topography and function of migratory phases remain unclear.In contrast to antigen-specific contacts, in vivo interactions between T cells and DC that do not present cognate antigen are Due to their intrinsic dynamics coupled to signal i...
