TY  - JOUR
A1  - Geissinger, Eva
A1  - Sadler, Petra
A1  - Roth, Sabine
A1  - Grieb, Tina
A1  - Puppe, Bernhard
A1  - Mueller, Nora
A1  - Reimer, Peter
A1  - Vetter-Kauczok, Claudia S.
A1  - Wenzel, Joerg
A1  - Bonzheim, Irina
A1  - Ruediger, Thomas
A1  - Mueller-Hermelink, Hans Konrad
A1  - Rosenwald, Andreas
T1  - Disturbed expression of the T-cell receptor/CD3 complex and associated signaling molecules in CD30(+) T-cell lymphoproliferations
N2  - Background CD30+ T-cell lymphoproliferations comprise a spectrum of clinically heterogeneous entities, including systemic anaplastic large cell lymphomas (ALK- and ALK+) and primary cutaneous CD30+ T-cell lymphoproliferative disorders. While all these entities are characterized by proliferation of highly atypical, anaplastic CD30+ T cells, the expression of T-cell specific antigens in the tumor cells is not consistently detectable. Design and Methods We evaluated biopsies from 19 patients with primary cutaneous CD30+ lymphoproliferative disorders, 38 with ALK- and 33 with ALK+ systemic anaplastic large cell lymphoma. The biopsies were examined for the expression of T-cell receptoraβ/CD3 complex (CD3γ, δ, ε, ζ), transcription factors regulating T-cell receptor expression (ATF1, ATF2, TCF-1, TCF-1a/LEF-1, Ets1), and molecules of T-cell receptor-associated signaling cascades (Lck, ZAP-70, LAT, bcl-10, Carma1, NFATc1, c-Jun, c-Fos, Syk) using immunohistochemistry. Results In comparison to the pattern in 20 peripheral T-cell lymphomas, not otherwise specified, we detected a highly disturbed expression of the T-cell receptor/CD3 complex, TCF-1, TCF- 1a/LEF-1, Lck, ZAP-70, LAT, NFATc1, c-Jun, c-Fos and Syk in most of the systemic anaplastic large cell lymphomas. In addition, primary cutaneous CD30+ lymphoproliferative disorders showed such a similar expression pattern to that of systemic anaplastic large cell lymphomas, that none of the markers we investigated can reliably distinguish between these CD30+ T-cell lymphoproliferations. Conclusions Severely altered expression of the T-cell receptor/CD3 complex, T-cell receptor-associated transcription factors and signal transduction molecules is a common characteristic of systemic and cutaneous CD30+ lymphoproliferations, although the clinical behavior of these entities is very different. Since peripheral T-cell lymphomas, not otherwise specified retain the full expression program required for functioning T-cell receptor signaling, the differential expression of a subset of these markers might be of diagnostic utility in distinguishing peripheral T-cell lymphomas, not otherwise specified from the entire group of CD30+ lymphoproliferations.
KW  - Medizin
KW  - systemic and cutaneous CD30+ lymphoproliferations
KW  - anaplastic large cell lymphoma
KW  - lymphomatoid papulosis
KW  - ALCL
KW  - LyP
KW  - TCR
Y1  - 2010
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68179
ER  - 
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
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-111038
ER  -