MethodsĬells were obtained from the blood of normal healthy donors at the Mayo Clinic Division of Transfusion Medicine according to institutional guidelines and informed consent in accordance with the Declaration of Helsinki. The multifocal character of the synapse, the requirement for active membrane segregation, the formation of the DC–T-cell synapse even in the absence of antigen, 30 and the unique DC role in immunity prompted us to investigate the changes in membrane structure in the course of interactions of human DCs with human T cells. 28 Even though changes in membrane structure have been implicated in the formation of multifocal synapses, 29 no available model of membrane organization explains how segregation develops and is maintained. 27 In addition, recent evidence suggests that mechanical TCR entrapment into segregated microdomains of the synapse is required for optimal T-cell activation. 26 Microdomain segregation could be important for the physical separation of ligands and receptors in the membrane plane such separation appears essential in preventing the cis-acting inhibition, such as that observed within the Notch family ligands and receptors during DC–T-cell interaction. In contrast to the unifocal T-cell–B-cell synapse, the structure of the DC–T-cell interaction site, studied mostly in murine cells, appears “immature” or “multifocal,” containing numerous segregated microdomains. 18-20 Most studies of the synapse have focused on those formed between T cells and B cells 21-25 consequently, the synapse between T cells and DCs has been studied to a much lesser extent. 14-17 Consequently, the full function of the synapse has been modified to include directed cytokine secretion, enhanced secondary signals, or internalization of TCRs. 12, 13 The initial idea that immunologic synapses mediate T-cell activation has been challenged by the finding that T-cell receptor (TCR)–mediated signaling precedes or is independent of synapse formation.
Early response to cell-cell contact includes the formation of a large macromolecular membrane assembly: the immunologic synapse 10, 11 and the consequent cell polarization. T cells are activated through cell-cell contact and by soluble molecules.
0 kommentar(er)
