Early cytoskeletal rearrangement during dendritic cell maturation enhances synapse formation and Ca(2+) signaling in CD8(+) T cells.
The interplay between dendritic cells (DC) and T cells is a dynamic process critically depending on DC maturation. Ca(2+) influx is one of the initial events occurring during DC/T cell contacts. To determine how DC maturation influences DC/T cell contacts, time-lapse video microscopy was established using TCR-transgenic CD8(+) T cells from P14 mice. DC maturation shifted DC/T cell contacts from short-lived interactions with transient Ca(2+) influx in T cells to long-lasting interactions and sustained Ca(2+) influx of 30 min and more. Follow-up of DC/T cell interactions after 2 h using confocal microscopy revealed that long-lasting Ca(2+) responses in T cells were preferentially associated with the formation of an immunological synapse involving CD54 and H2-K(b) at the DC/T cell interface. Such synapse formation preceded MHC or B7 up-regulation, since DC developed into potent Ca(2+) stimulators 7 h after initiation of maturation. Instead, the enhanced capacity of 7 h-matured DC to induce sustained Ca(2+) responses in CD8(+) T cells is critically dependent on the polarization and rearrangement of the cytoskeleton, as shown by Clostridium difficile toxin B inhibitor experiments. These data indicate that already very early after receiving a maturation stimulus, DC display enhanced cytoskeletal activity resulting in the rapid formation of immunological synapses and effective CD8(+) T cell stimulation.
Averbeck
Marco
M
Department of Dermatology, University of Leipzig, Leipzig, Germany. marco.averbeck@medizin.uni-leipzig.de
Braun
Thorsten
T
Pfeifer
Gunther
G
Sleeman
Jonathan
J
Dudda
Jan
J
Martin
Stefan F
SF
Kremer
Bernhard
B
Aktories
Klaus
K
Simon
Jan C
JC
Termeer
Christian
C
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002450:Cell Communication / Q000276:immunology; D002465:Cell Movement; D016764:Cell Polarity; D003599:Cytoskeleton / Q000502:physiology*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D018715:Microscopy, Video; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D015398:Signal Transduction / Q000276:immunology*
D000949:Histocompatibility Antigens Class II; D011948:Receptors, Antigen, T-Cell; D018799:Intercellular Adhesion Molecule-1; D002118:Calcium