Abstract
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.
Original language | English |
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Pages (from-to) | 115-126 |
Number of pages | 12 |
Journal | Clinical Immunology |
Volume | 152 |
Issue number | 1-2 |
DOIs | |
State | Published - May 2014 |
Keywords
- CD8
- IL-12
- Multiple sclerosis
- Regulatory
- T cells