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Serum CD95 of relapsing remitting multiple sclerosis patients protects from CD95-mediated apoptosis
F Zipp1, K Otzelberger, J Dichgans
1Department of Neurology, University of Tübingen, Germany. frauke.zipp@uni-tuebingen.de
Abstract:
Failure of CD95-mediated apoptosis as a potential negative regulatory mechanism of T cell expansion may be involved in T cell-mediated autoimmune diseases such as multiple sclerosis (MS). Recently, soluble CD95 has been shown to be elevated in MS patients with active disease. Here, we report that the sera of MS patients inhibit CD95 ligand-induced apoptosis of susceptible target cells in a concentration-dependent manner and dependent on the amount of serum CD95 levels. Thus, MS sera contain biologically active inhibitors of T cell apoptosis that may allow for prolonged abnormal immune responses.
Insights
Serum from multiple sclerosis patients contains inhibitors that block T cell death. This may contribute to prolonged immune responses in multiple sclerosis (MS) by preventing normal regulation of T cell expansion.
Area of Science:
- Immunology
- Neuroimmunology
- Autoimmunity
Background:
- T cell apoptosis, regulated by CD95, is crucial for controlling immune responses.
- Dysregulation of T cell apoptosis is implicated in autoimmune diseases like multiple sclerosis (MS).
- Elevated levels of soluble CD95 have been observed in MS patients with active disease.
Purpose of the Study:
- To investigate the potential role of serum factors in inhibiting CD95-mediated apoptosis in MS.
- To determine if serum CD95 levels correlate with the inhibitory activity on T cell apoptosis.
Main Methods:
- Analysis of sera from multiple sclerosis patients.
- Assay to measure CD95 ligand-induced apoptosis in susceptible target cells.
- Quantification of soluble CD95 levels in patient sera.
Main Results:
- Sera from MS patients demonstrated a concentration-dependent inhibition of CD95 ligand-induced apoptosis.
- The inhibitory effect of MS sera on apoptosis was directly related to the levels of soluble CD95 present.
- These findings indicate the presence of biologically active inhibitors of T cell apoptosis in MS sera.
Conclusions:
- Serum from MS patients contains active inhibitors of T cell apoptosis.
- These inhibitors, associated with soluble CD95 levels, may contribute to aberrant T cell expansion in MS.
- This mechanism could play a role in the pathogenesis of T cell-mediated autoimmune diseases like multiple sclerosis.