Inhibition of calpain attenuates encephalitogenicity of MBP-specific T cells
Version of Record online: 17 JUL 2009
© 2009 The Authors. Journal Compilation © 2009 International Society for Neurochemistry
Journal of Neurochemistry
Volume 110, Issue 6, pages 1895–1907, September 2009
How to Cite
Guyton, M. K., Brahmachari, S., Das, A., Samantaray, S., Inoue, J., Azuma, M., Ray, S. K. and Banik, N. L. (2009), Inhibition of calpain attenuates encephalitogenicity of MBP-specific T cells. Journal of Neurochemistry, 110: 1895–1907. doi: 10.1111/j.1471-4159.2009.06287.x
- Issue online: 3 SEP 2009
- Version of Record online: 17 JUL 2009
- Received January 27, 2009; revised manuscript received July 6, 2009; accepted July 9, 2009.
- experimental autoimmune encephalomyelitis;
- myelin basic protein-specific T cells
Multiple sclerosis (MS) is a T-cell mediated autoimmune disease of the CNS, possessing both immune and neurodegenerative events that lead to disability. Adoptive transfer (AT) of myelin basic protein (MBP)-specific T cells into naïve female SJL/J mice results in a relapsing–remitting (RR) form of experimental autoimmune encephalomyelitis (EAE). Blocking the mechanisms by which MBP-specific T cells are activated before AT may help characterize the immune arm of MS and offer novel targets for therapy. One such target is calpain, which is involved in activation of T cells, migration of immune cells into the CNS, degradation of axonal and myelin proteins, and neuronal apoptosis. Thus, the hypothesis that inhibiting calpain in MBP-specific T cells would diminish their encephalitogenicity in RR-EAE mice was tested. Incubating MBP-specific T cells with the calpain inhibitor SJA6017 before AT markedly suppressed the ability of these T cells to induce clinical symptoms of RR-EAE. These reductions correlated with decreases in demyelination, inflammation, axonal damage, and loss of oligodendrocytes and neurons. Also, calpain : calpastatin ratio, production of truncated Bid, and Bax : Bcl-2 ratio, and activities of calpain and caspases, and internucleosomal DNA fragmentation were attenuated. Thus, these data suggest calpain as a promising target for treating EAE and MS.