Neuroantigen-specific CD8+ regulatory T-cell function is deficient during acute exacerbation of multiple sclerosis

Ethan J. Baughman, Jason P. Mendoza, Sterling B. Ortega, Chris L. Ayers, Benjamin Greenberg, Elliot Frohman, Nitin J. Karandikar

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system (CNS). MS is thought to be T-cell-mediated, with prior research predominantly focusing on CD4+ T-cells. There is a high prevalence of CNS-specific CD8+ T-cell responses in MS patients and healthy subjects. However, the role of neuroantigen-specific CD8+ T-cells in MS is poorly understood, with the prevalent notion that these may represent pathogenic T-cells. We show here that healthy subjects and MS patients demonstrate similar magnitudes of CD8+ and CD4+ T-cell responses to various antigenic stimuli. Interestingly, CD8+ T-cells specific for CNS autoantigens, but not those specific for control foreign antigens, exhibit immune regulatory ability, suppressing proliferation of CD4+CD25- T-cells when stimulated by their cognate antigen. While CD8+ T-cell-mediated immune suppression is similar between healthy subjects and clinically quiescent treatment-naïve MS patients, it is significantly deficient during acute exacerbation of MS. Of note, the recovery of neuroantigen-specific CD8+ T-cell suppression correlates with disease recovery post-relapse. These studies reveal a novel immune suppressor function for neuroantigen-specific CD8+ T-cells that is clinically relevant in the maintenance of peripheral tolerance and the intrinsic regulation of MS immune pathology.

Original languageEnglish (US)
Pages (from-to)115-124
Number of pages10
JournalJournal of Autoimmunity
Volume36
Issue number2
DOIs
StatePublished - Mar 1 2011

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Keywords

  • CD8
  • Exacerbation
  • Immune regulation
  • Multiple sclerosis
  • Suppressor
  • T

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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