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CD95 expression and CD95-mediated apoptosis of T cells in multiple sclerosis. No differences from normal individuals
1Department of Neurology, University of Tübingen, Germany. frauke.zipp@uni-tuebingen.de
Abstract:
CD95-mediated apoptosis is a potent endogenous pathway of T cell elimination that has been suggested to be altered in multiple sclerosis (MS). MS is associated with the HLA-DR2, Dw2, DQ6 HLA class II haplotype. We have previously reported that T cell lines from HLA-DR2-positive individuals show enhanced production of tumor necrosis factor (TNF), a cytokine homologous to CD95 ligand, in response to specific antigen. Here we have studied CD95 expression and susceptibility to CD95-mediated apoptosis in peripheral blood mononuclear cells (PBMC) and activated T cells of 20 healthy individuals and 20 MS patients, half of whom were HLA-DR2-positive. MS patients did not differ from healthy individuals in either parameter. There was also no difference in CD95 expression or CD95-mediated apoptosis when MS patients and healthy individuals were grouped and compared according to HLA-DR status. These data reveal no differential regulation of PBMC/T cell apoptosis induced by CD95 receptor ligation in MS and show no impact of HLA-DR2 status on PBMC/T cell susceptibility to the same apoptotic stimulus. However, to assess the contribution of T cell apoptosis to the pathogenesis of MS further studies on other details of the complex system leading to T cell apoptosis are required.
Insights
Multiple sclerosis (MS) patients do not show altered CD95-mediated apoptosis in T cells compared to healthy individuals. HLA-DR2 status also does not impact T cell apoptosis susceptibility in MS.
Area of Science:
- Immunology
- Neuroimmunology
- Cell Biology
Background:
- CD95-mediated apoptosis is a key T cell elimination pathway.
- This pathway's alteration is hypothesized in Multiple Sclerosis (MS).
- MS is linked to the HLA-DR2 haplotype, associated with increased TNF production in T cells.
Purpose of the Study:
- To investigate CD95 expression and apoptosis susceptibility in MS patients.
- To determine if HLA-DR2 status influences these parameters in MS.
- To clarify the role of T cell apoptosis in MS pathogenesis.
Main Methods:
- Studied CD95 expression and CD95-mediated apoptosis.
- Utilized peripheral blood mononuclear cells (PBMC) and activated T cells.
- Compared 20 MS patients and 20 healthy individuals, stratified by HLA-DR2 status.
Main Results:
- No significant differences in CD95 expression or apoptosis were found between MS patients and healthy controls.
- HLA-DR2 status did not affect CD95 expression or apoptosis susceptibility in either group.
- These findings indicate no differential regulation of CD95-induced T cell apoptosis in MS.
Conclusions:
- CD95 receptor ligation does not appear differentially regulated in MS PBMCs/T cells.
- HLA-DR2 status has no discernible impact on T cell apoptosis susceptibility in this context.
- Further research into complex T cell apoptosis systems is needed to fully understand MS pathogenesis.