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 M Greenberg; Elliot M Frohman; Nitin J Karandikar

doi:10.1016/j.jaut.2010.12.003

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

Journal article

Open access

Peer reviewed

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 M Greenberg, Elliot M Frohman and Nitin J Karandikar

Journal of autoimmunity, Vol.36(2), pp.115-124

2011

DOI: 10.1016/j.jaut.2010.12.003

PMCID: PMC3046327

PMID: 21257291

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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.

Exacerbation

Suppressor

Multiple sclerosis

Immune regulation

CD8

T reg

Details

Title: Subtitle: Neuroantigen-specific CD8+ regulatory T-cell function is deficient during acute exacerbation of multiple sclerosis
Creators: Ethan J Baughman - Department of Pathology, UT Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA
Jason P Mendoza - Department of Pathology, UT Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA
Sterling B Ortega - Department of Pathology, UT Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA
Chris L Ayers - Department of Pathology, UT Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA
Benjamin M Greenberg - Department of Neurology, UT Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA
Elliot M Frohman - Department of Neurology, UT Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA
Nitin J Karandikar - Department of Pathology, UT Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA
Resource Type: Journal article
Publication Details: Journal of autoimmunity, Vol.36(2), pp.115-124
DOI: 10.1016/j.jaut.2010.12.003
PMID: 21257291
PMCID: PMC3046327
NLM abbreviation: J Autoimmun
ISSN: 0896-8411
eISSN: 1095-9157
Publisher: Elsevier Ltd
Language: English
Date published: 2011
Academic Unit: Pathology
Record Identifier: 9984047849702771

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