title: Calcium Signalling Triggered by NAADP in T Cells Determines Cell Shape and Motility During Immune Synapse Formation.
abstract: Nicotinic acid adenine dinucleotide phosphate (NAADP) has been implicated as an initial Ca2+trigger in T cell Ca2+signalling, but its role in formation of the immune synapse in CD4+effector T cells has not been analysed. CD4+T cells are activated by the interaction with peptide-MHCII complexes on the surface of antigen-presenting cells. Establishing a two-cell system including primary rat CD4+T cells specific for myelin basic protein and rat astrocytes enabled us to mirror this activation processin vitroand to analyse Ca2+signalling, cell shape changes and motility in T cells during formation and maintenance of the immune synapse. After immune synapse formation, T cells showed strong, antigen-dependent increases in free cytosolic calcium concentration ([Ca2+]i). Analysis of cell shape and motility revealed rounding and immobilization of T cells depending on the amplitude of the Ca2+signal. NAADP-antagonist BZ194 effectively blocked Ca2+signals in T cells evoked by the interaction with antigen-presenting astrocytes. BZ194 reduced the percentage of T cells showing high Ca2+signals thereby supporting the proposed trigger function of NAADP for global Ca2+signalling. Taken together, the NAADP signalling pathway is further confirmed as a promising target for specific pharmacological intervention to modulate T cell activation.
authors.affiliation: The Calcium Signalling Group, Department of Biochemistry and Signal Transduction, University Medical Centre Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.
authors.forename: Merle
authors.initials: M
authors.lastname: Nebel
authors.affiliation: Wolfson Laboratory of Medicinal Chemistry, Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath BA2 7AY, UK.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Institute for Multiple Sclerosis Research, Department of Neuroimmunology, Gemeinnützige Hertie-Stiftung and University Medical Centre Göttingen, 37073 Göttingen, Germany.
authors.forename: Francesca
authors.initials: F
authors.lastname: Odoardi
authors.affiliation: Institute for Multiple Sclerosis Research, Department of Neuroimmunology, Gemeinnützige Hertie-Stiftung and University Medical Centre Göttingen, 37073 Göttingen, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Flügel
authors.affiliation: Wolfson Laboratory of Medicinal Chemistry, Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath BA2 7AY, UK.
authors.forename: Barry V L
authors.initials: BV
authors.lastname: Potter
authors.affiliation: The Calcium Signalling Group, Department of Biochemistry and Signal Transduction, University Medical Centre Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany; Department of Biochemistry and Molecular Cell Biology, University Medical Centre Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.
authors.forename: Andreas H
authors.initials: AH
authors.lastname: Guse
keywords: Ca2+ Signalling; Cytoskeleton; Live Cell Imaging; NAADP; T Cell Activation