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Modulation of CD4+ T-cell activation by CD95 co-stimulation
- Source :
- Cell Death & Differentiation. 18:619-631
- Publication Year :
- 2010
- Publisher :
- Springer Science and Business Media LLC, 2010.
-
Abstract
- CD95 is a dual-function receptor that exerts pro- or antiapoptotic effects depending on the cellular context, the state of activation, the signal threshold and the mode of ligation. In this study, we report that CD95 engagement modulates TCR/CD3-driven signaling pathways in resting T lymphocytes in a dose-dependent manner. While high doses of immobilized CD95 agonists silence T cells, lower concentrations augment activation and proliferation. We analyzed the co-stimulatory capacity of CD95 in detail in resting human CD4(+) T cells, and demonstrate that low-dose ligand-induced co-internalization of CD95 and TCR/CD3 complexes enables non-apoptotic caspase activation, the prolonged activation of MAP kinases, the upregulation of antiapoptotic proteins associated with apoptosis resistance, and the activation of transcription factors and cell-cycle regulators for the induction of proliferation and cytokine production. We propose that the levels of CD95L on antigen-presenting cells (APCs), neighboring T cells or epithelial cells regulate inhibitory or co-stimulatory CD95 signaling, which in turn is crucial for fine-tuning of primary T-cell activation.
- Subjects :
- CD4-Positive T-Lymphocytes
Fas Ligand Protein
CD3 Complex
medicine.medical_treatment
CD3
Receptors, Antigen, T-Cell
Antigen-Presenting Cells
Cell Cycle Proteins
chemical and pharmacologic phenomena
Biology
Lymphocyte Activation
Downregulation and upregulation
Co-stimulation
medicine
Guanine Nucleotide Exchange Factors
Humans
Cytotoxic T cell
fas Receptor
Phosphorylation
Molecular Biology
Transcription factor
Cell Proliferation
Mitogen-Activated Protein Kinase Kinases
Original Paper
T-cell receptor
Antibodies, Monoclonal
Nuclear Proteins
hemic and immune systems
Cell Biology
Cell biology
Immobilized Proteins
Cytokine
Caspases
biology.protein
Cytokines
Signal transduction
Signal Transduction
Subjects
Details
- ISSN :
- 14765403 and 13509047
- Volume :
- 18
- Database :
- OpenAIRE
- Journal :
- Cell Death & Differentiation
- Accession number :
- edsair.doi.dedup.....f39ea8f43589d84625c991b4e37d6961