Efficiency of T-cell costimulation by CD80 and CD86 cross-linking correlates with calcium entry
Markus Thiel, Melodie-Jo Wolfs, Stefan Bauer, Anna S Wenning, Tanja Burckhart, Eva C Schwarz, Andrew M Scott, Christoph Renner, Markus Hoth
IMMUNOLOGY | WILEY | Published : 2010
Costimulation is a fundamental principle of T-cell activation. In addition to T-cell receptor engagement, the interaction between CD80 and/or CD86 with CD28 and/or cytotoxic T-lymphocyte antigen 4 (CTLA-4) receptors is required to regulate T-cell activation and tolerance. While the importance of costimulation is clearly established, the exact molecular mechanism is unknown. We demonstrate that T-cell proliferation and the ability of CD8(+) T-effector cells to kill were enhanced slightly by CD80 but dramatically by CD86 costimulation. To further analyse the cellular process of costimulation, we developed a single-cell assay to analyse Ca(2+) signals following costimulation with bi-specific an..View full abstract
Awarded by Deutsche Forschungsgemeinschaft
Research carried out for this study with human material has been approved by the local ethics committee. The authors have no conflict of interest. We thank Bettina Strau ss and Anja Ludes for excellent technical support. We thank Varsha Pattu for reading and correcting the manuscript. This project was supported in part by the Ludwig Institute for Cancer Research, NY, USA (to A.M.S. and C.R.), Oncosuisse (to C.R.), the Deutsche Forschungsgemeinschaft (SFB 530, project A3, DFG grant HO 2190/1-2, and Graduate Colleges 'Molecular, physiological and pharmacological analysis of cellular membrane transport' and 'Calcium signaling and nanodomains', all to M.H.) and a competitive intra-faculty grant from HOMFOR (to E.C.S.).