TY  - JOUR
A1  - Schneider-Schaulies, Sibylle
A1  - Mueller, Nora
A1  - Avota, Elita
A1  - Collenburg, Lena
A1  - Grassmé, Heike
T1  - Neutral Sphingomyelinase in Physiological and Measles Virus Induced T Cell Suppression
N2  - T cell paralysis is a main feature of measles virus (MV) induced immunosuppression. MV contact mediated activation of sphingomyelinases was found to contribute to MV interference with T cell actin reorganization. The role of these enzymes in MV-induced inhibition of T cell activation remained equally undefined as their general role in regulating immune synapse (IS) activity which relies on spatiotemporal membrane patterning. Our study for the first time reveals that transient activation of the neutral sphingomyelinase 2 (NSM2) occurs in physiological co-stimulation of primary T cells where ceramide accumulation is confined to the lamellum (where also NSM2 can be detected) and excluded from IS areas of high actin turnover. Genetic ablation of the enzyme is associated with T cell hyper-responsiveness as revealed by actin dynamics, tyrosine phosphorylation, Ca2+-mobilization and expansion indicating that NSM2 acts to suppress overshooting T cell responses. In line with its suppressive activity, exaggerated, prolonged NSM2 activation as occurring in co-stimulated T cells following MV exposure was associated with aberrant compartmentalization of ceramides, loss of spreading responses, interference with accumulation of tyrosine phosphorylated protein species and expansion. Altogether, this study for the first time reveals a role of NSM2 in physiological T cell stimulation which is dampening and can be abused by a virus, which promotes enhanced and prolonged NSM2 activation to cause pathological T cell suppression.
KW  - T cells
KW  - cell membrane
KW  - actins
KW  - enzymes
KW  - T cell receptors
KW  - flow cytometry
KW  - genetic interference
KW  - tyrosine
Y1  - 2014
UR  - https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/11103
UR  - https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-111038
ER  -