Multiple Sclerosis Resource Centre

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Disease exacerbation of multiple sclerosis is characterized by loss of terminally differentiated autoregulatory CD8 + T cells

Khrishen Cunnusamy, Ethan J. Baughman, Jorge Franco, Sterling B. Ortega, Sushmita Sinha, Parul Chaudhary, Benjamin M. Greenberg, Elliot M. Frohman, Nitin J. Karandikar

Clinical Immunology, Volume 152, Issues 1–2, May–June 2014, Pages 115–126

Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system (CNS). Although its etiology remains unknown, pathogenic T cells are thought to underlie MS immune pathology. We recently showed that MS patients harbor CNS-specific CD8 + Tregs that are deficient during disease relapse. We now demonstrate that CNS-specific CD8 + Tregs were cytolytic and could eliminate pathogenic CD4 + T cells. These CD8 + Tregs were present primarily in terminally differentiated (CD27 −, CD45RO −) subset and their suppression was IFNγ, perforin and granzyme B-dependent. Interestingly, MS patients with acute relapse displayed a significant loss in terminally differentiated CD8 + T cells, with a concurrent loss in expression of perforin and granzyme B. Pre-treatment of exacerbation-derived CD8 + T cells with IL-12 significantly restored suppressive capability of these cells through upregulation of granzyme B. Our studies uncover immune-suppressive mechanisms of CNS-specific CD8 + Tregs, and may contribute to design of novel immune therapies for MS.

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About the Editors

  • Prof Timothy Vartanian

    Timothy Vartanian, Professor at the Brain and Mind Research Institute and the Department of Neurology, Weill Cornell Medical College, Cornell...
  • Dr Claire S. Riley

    Claire S. Riley, MD is an assistant attending neurologist and assistant professor of neurology in the Neurological Institute, Columbia University,...
  • Dr Rebecca Farber

    Rebecca Farber, MD is an attending neurologist and assistant professor of neurology at the Neurological Institute, Columbia University, in New...

This online Resource Centre has been made possible by a donation from EMD Serono, Inc., a business of Merck KGaA, Darmstadt, Germany.

Note that EMD Serono, Inc., has no editorial control or influence over the content of this Resource Centre. The Resource Centre and all content therein are subject to an independent editorial review.

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