CD95 resistance in long-term-activated T lymphocytes
Long-term-activated T cells can be found in autoimmune diseases such as rheumatoid arthritis and multiple sclerosis and are resistant to CD95-induced apoptosis. The major aim of this work was to investigate the mechanisms of CD95 resistance in order to find new molecular targets for the therapy of these diseases. Long-term-activated T cells show constitutive caspase activation, usually a sign for apoptosis, but are resistant towards CD95-induced cell death. Caspase-8 has been shown to interact with components of the NF-kB signaling pathway within lipid rafts during the first steps of NF-kB signaling, which can be pro- or antiapoptotic. Therefore, the goal of this work was to show, whether NF-kB plays a role in the development of CD95 resistance in long-term-activated T cells or not. For this purpose, in vitro-generated, short- and long-term-activated T cells were compared by EMSA and analysis of lipid raft composition to get a better understanding of constitutive lipid raft localization of signaling mediators important for CD95-induced apoptosis, TCR- and NF-kB signaling. Investigation of NF-kB activity by EMSA and inhibition of the pathway demonstrated that the activation status of NF-kB cannot be related to CD95 resistance in long-term-activated T cells. However, analysis of lipid raft composition in both cell types revealed differences in constitutive raft localization of TCR signaling proteins, such as reduced recruitment of Zap-70.
Erstellung / Fertigstellung
Normierte SchlagwörterCaspasen [GND]
Nuklearfaktor Kappa B [GND]
Antigens, CD95 [MeSH]