Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

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 process in vitro and 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.

Original publication

DOI

10.1166/msr.2015.1045

Type

Journal article

Journal

Messenger (Los Angel)

Publication Date

06/2015

Volume

4

Pages

104 - 111

Keywords

Ca2+ Signalling, Cytoskeleton, Live Cell Imaging, NAADP, T Cell Activation