CTLA‐4 disrupts ZAP70 microcluster formation with reduced T cell/APC dwell times and calcium mobilization
Open Access
- 21 December 2007
- journal article
- research article
- Published by Wiley in European Journal of Immunology
- Vol. 38 (1) , 40-47
- https://doi.org/10.1002/eji.200737423
Abstract
CTLA-4 is a co-receptor that modulates the threshold of T cell activation and autoimmunity. We previously showed that CTLA-4 reverses the TCR-mediated stop signal needed for T cell/APC interactions [Schneider et al., Science 2006, 313: 1972]. In this study, using a different T cell system, we show that CTLA-4 expression changed the behavior of T8.1 T cells by reducing the contact time between T cell and APC, preventing re-inforced contacts, and reducing the contact area at the immunological synapse. This led to a major reduction in Ca2+ influx/mobilization and interleukin-2 production. Further, anti-CD3/CTLA-4 increased T cell motility on antibody-coated glass slides, concurrent with an abrogation of ZAP70 microcluster formation. Our findings further support a role for CTLA-4 in limiting the interaction between T cell and APC that is needed for optimal activation.Keywords
This publication has 39 references indexed in Scilit:
- Programmed Death-1 Ligand 1 Interacts Specifically with the B7-1 Costimulatory Molecule to Inhibit T Cell ResponsesImmunity, 2007
- Modeling CTLA4 -linked autoimmunity with RNA interference in miceProceedings of the National Academy of Sciences, 2006
- La synapse immunologique : des modèles aux réalitésmédecine/sciences, 2006
- T Cell Receptor-Proximal Signals Are Sustained in Peripheral Microclusters and Terminated in the Central Supramolecular Activation ClusterImmunity, 2006
- Regulatory T cells inhibit stable contacts between CD4+ T cells and dendritic cells in vivoThe Journal of Experimental Medicine, 2006
- Newly generated T cell receptor microclusters initiate and sustain T cell activation by recruitment of Zap70 and SLP-76Nature Immunology, 2005
- B7-1 and B7-2 Selectively Recruit CTLA-4 and CD28 to the Immunological SynapseImmunity, 2004
- Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune diseaseNature, 2003
- Negative Regulation of T Cell Receptor–Lipid Raft Interaction by Cytotoxic T Lymphocyte–associated Antigen 4The Journal of Experimental Medicine, 2003
- T cell receptor ligation induces the formation of dynamically regulated signaling assembliesThe Journal of cell biology, 2002