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Autoreactive CD8+ T cells in multiple sclerosis: a new target for therapy?
1MRC Human Immunology Unit and Department of Clinical Neurology, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, UK.
Brain : a Journal of Neurology
|June 25, 2005
Summary
CD8(+) T cells, often overlooked, may play a significant role in multiple sclerosis (MS) pathogenesis. Emerging evidence suggests these cells, alongside CD4(+) T cells, are involved in MS, prompting a reevaluation of therapeutic strategies.
Area of Science:
- Neuroimmunology
- Autoimmune Diseases
Background:
- Multiple sclerosis (MS) is a chronic autoimmune disease affecting over 1 million people globally.
- Traditionally, CD4(+) T helper cells have been implicated in MS immunopathogenesis, supported by genetic links to MHC class II alleles and their role in experimental autoimmune encephalomyelitis (EAE).
- Therapeutic strategies targeting CD4(+) T cells have shown limited success in MS patients and sometimes worsen disease.
Purpose of the Study:
- To explore the emerging evidence for the role of CD8(+) T cells in multiple sclerosis.
- To re-evaluate the long-standing focus on CD4(+) T cells in MS pathogenesis.
- To consider CD8(+) T cells as a potential target for new therapeutic approaches.
Main Methods:
- Review of existing literature on T cell involvement in multiple sclerosis.
- Analysis of genetic associations with MHC class I alleles in MS.
- Examination of findings from CD8(+) T cell-induced animal models.
Main Results:
- Genetic associations with MHC class I alleles are established in MS.
- Both CD8(+) and CD4(+) T cells infiltrate the central nervous system and undergo clonal expansion in MS plaques.
- CD8(+) T cell-induced animal models exhibit similarities to MS, particularly in lesion distribution within the brain.
Conclusions:
- CD8(+) T cells, previously underrated, warrant consideration for their role in multiple sclerosis.
- The findings suggest that CD8(+) T cells may be a crucial, yet underappreciated, component of MS immunopathogenesis.
- New therapeutic strategies for multiple sclerosis should consider targeting CD8(+) T cells.