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

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 IFN?, 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.

SUBMITTER: Cunnusamy K

PROVIDER: S-EPMC4024444 | biostudies-literature | 2014 May-Jun

REPOSITORIES: biostudies-literature

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

Cunnusamy Khrishen K Baughman Ethan J EJ Franco Jorge J Ortega Sterling B SB Sinha Sushmita S Chaudhary Parul P Greenberg Benjamin M BM Frohman Elliot M EM Karandikar Nitin J NJ

Clinical immunology (Orlando, Fla.) 20140320 1-2

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-, ...[more]

PMID: 24657764

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Dataset Information

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

Publications

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

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