A dynamic immunological synapse mediates homeostatic TCR-dependent and -independent signaling.
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".
Storim
Julian
J
Department of Dermatology and Rudolf Virchow Center for Experimental Biomedicine, University of Würzburg, Germany.
Bröcker
Eva B
EB
Friedl
Peter
P
D000818:Animals; D017252:CD3 Complex / Q000276:immunology; D002450:Cell Communication / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology; D016764:Cell Polarity / Q000276:immunology; D003094:Collagen / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D006649:Histocompatibility Antigens / Q000276:immunology; D006706:Homeostasis / Q000276:immunology; D021621:Imaging, Three-Dimensional; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D019000:Phosphotyrosine / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D017252:CD3 Complex; D006649:Histocompatibility Antigens; D016169:Lymphocyte Function-Associated Antigen-1; D011948:Receptors, Antigen, T-Cell; D019000:Phosphotyrosine; D003094:Collagen