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Lack of TIM-3 immunoregulation in multiple sclerosis
Li Yang1, David E Anderson, Juhi Kuchroo
1Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|March 21, 2008
Summary
Multiple sclerosis (MS) patients show impaired TIM-3 immune regulation. Therapies like glatiramer acetate and IFN-beta restore TIM-3 function, suggesting a therapeutic mechanism for MS treatment.
Area of Science:
- Immunology
- Neuroimmunology
- Cellular Immunology
Background:
- Multiple sclerosis (MS) is a central nervous system inflammatory disease impacting T cells.
- TIM-3 is a key regulator of T helper 1 (Th1) cells and immune tolerance.
- Dysregulation of T cell function is implicated in MS pathogenesis.
Purpose of the Study:
- To investigate the function of TIM-3 on T cells from healthy individuals and MS patients.
- To explore the impact of TIM-3 blockade on T cell immune responses in MS.
- To determine if MS therapies can restore TIM-3 mediated immunoregulation.
Main Methods:
- Generated a novel monoclonal antibody (mAb) against human TIM-3.
- Isolated and analyzed ex vivo CD4(+) T cells from healthy subjects and MS patients.
- Assessed IFN-gamma secretion following TIM-3 blockade during T cell stimulation.
- Evaluated TIM-3 expression levels and kinetics in T cells.
Main Results:
- TIM-3 blockade enhanced IFN-gamma secretion in healthy controls but not in untreated MS patients, indicating a regulatory defect.
- This TIM-3 functional defect was reversed by treatment with glatiramer acetate or IFN-beta.
- Reduced T cell TIM-3 expression and altered kinetics were observed in untreated MS patients, with restoration in treated patients.
Conclusions:
- A defect in TIM-3 mediated immunoregulation contributes to T cell dysfunction in untreated MS.
- Approved MS therapies, glatiramer acetate and IFN-beta, may restore TIM-3 function.
- Restoration of TIM-3 immunoregulation is a potential mechanism for MS treatment.
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