Calcium Signalling Triggered by NAADP in T Cells Determines Cell Shape and Motility During Immune Synapse Formation
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Calcium Signalling Triggered by NAADP in T Cells Determines Cell Shape and Motility During Immune Synapse Formation. / Nebel, Merle; Zhang, Bo; Odoardi, Francesca; Flügel, Alexander; Potter, Barry V L; Guse, Andreas H.
In: Messenger (Los Angel), Vol. 4, No. 1, 06.2015, p. 104-111.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Calcium Signalling Triggered by NAADP in T Cells Determines Cell Shape and Motility During Immune Synapse Formation
AU - Nebel, Merle
AU - Zhang, Bo
AU - Odoardi, Francesca
AU - Flügel, Alexander
AU - Potter, Barry V L
AU - Guse, Andreas H
PY - 2015/6
Y1 - 2015/6
N2 - 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.
AB - 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.
U2 - 10.1166/msr.2015.1045
DO - 10.1166/msr.2015.1045
M3 - SCORING: Journal article
C2 - 27747143
VL - 4
SP - 104
EP - 111
JO - Messenger (Los Angel)
JF - Messenger (Los Angel)
SN - 2167-955X
IS - 1
ER -
