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 Greenberg, Elliot Frohman, Nitin J. Karandikar

Research output: Contribution to journalArticle

23 Scopus citations

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 languageEnglish (US)
Pages (from-to)115-126
Number of pages12
JournalClinical Immunology
Volume152
Issue number1-2
DOIs
StatePublished - May 2014

Keywords

  • CD8
  • IL-12
  • Multiple sclerosis
  • Regulatory
  • T cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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