Related Experiment Videos
Impaired apoptotic deletion of myelin basic protein-reactive T cells in patients with multiple sclerosis
Y C Zang1, M M Kozovska, J Hong
1Department of Neurology, Baylor College of Medicine, and Baylor-Methodist Multiple Sclerosis Center, Houston 77030, USA. jzang@bcm.tmc.edu
Abstract:
T cell responses to myelin basic protein (MBP) may play an important role in the pathogenesis of multiple sclerosis (MS). If MBP-reactive T cells are involved in the disease processes and undergo clonal activation and expansion, their precursor frequency would be increased in patients with MS. The frequency of MBP-reactive T cells is also influenced by regulatory mechanisms in vivo, including apoptotic deletion. In this study, we examined changes in the frequency of MBP-reactive T cells in patients with MS as a function of the apoptotic deletional mechanism in vivo, using a cell culture-based assay. A significantly increased frequency of MBP-reactive T cells was found in patients with MS relative to healthy individuals only when Fas-ligand antibody was used to block apoptosis. This result indicates that a significant proportion of MBP-reactive T cells are sensitive to apoptosis and are not deleted in vivo in patients with MS, as opposed to healthy individuals, thus suggesting a functional deficit in apoptotic deletional mechanism. Surviving Fas-sensitive MBP-reactive T cell lines represent distinct subpopulations preferentially recognizing the 111-139 region of MBP and exhibiting a Th2 cytokine profile. The findings are relevant to our understanding of regulation of MBP-reactive T cells in vivo in MS.
Insights
Multiple sclerosis (MS) patients show increased myelin basic protein (MBP)-reactive T cells when apoptosis is blocked. This suggests a defect in the natural removal of these disease-associated T cells in MS.
Area of Science:
- Immunology
- Neuroscience
- Cell Biology
Background:
- T cell responses to myelin basic protein (MBP) are implicated in multiple sclerosis (MS) pathogenesis.
- Regulatory mechanisms, such as apoptotic deletion, influence the frequency of MBP-reactive T cells.
Purpose of the Study:
- To investigate the frequency of MBP-reactive T cells in MS patients.
- To examine the role of apoptotic deletion in regulating MBP-reactive T cells in MS.
Main Methods:
- Utilized a cell culture-based assay to assess MBP-reactive T cell frequency.
- Employed Fas-ligand antibody to block apoptosis during T cell analysis.
Main Results:
- A significantly increased frequency of MBP-reactive T cells was observed in MS patients compared to healthy individuals when apoptosis was inhibited.
- These findings indicate that a substantial population of MBP-reactive T cells are sensitive to apoptosis but are not effectively deleted in vivo in MS patients.
- The surviving T cell lines recognized a specific region (111-139) of MBP and displayed a Th2 cytokine profile.
Conclusions:
- Suggests a functional deficit in the apoptotic deletional mechanism for MBP-reactive T cells in multiple sclerosis.
- Highlights the importance of apoptosis in regulating potentially pathogenic T cell responses in MS.
- Identified distinct subpopulations of Fas-sensitive MBP-reactive T cells involved in MS pathogenesis.