Immune regulation of multiple sclerosis by CD8+ T cells

Sushmita Sinha, Farah R. Itani, Nitin J. Karandikar

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

The role of CD8+ T cells in the process of autoimmune pathology has been both understudied and controversial. Multiple sclerosis (MS) is an inflammatory, demyelinating disorder of the central nervous system (CNS) with underlying T cell-mediated immunopathology. CD8+ T cells are the predominant T cells in human MS lesions, showing oligoclonal expansion at the site of pathology. It is still unclear whether these cells represent pathogenic immune responses or disease-regulating elements. Through studies in human MS and its animal model, experimental autoimmune encephalomyelitis (EAE), we have discovered two novel CD8+ T cell populations that play an essential immunoregulatory role in disease: (1) MHC class Ia-restricted neuroantigen-specific "autoregulatory" CD8+ T cells and (2) glatiramer acetate (GA/Copaxone®) therapy-induced Qa-1/HLA-E-restricted GA-specific CD8+ T cells. These CD8+ Tregs suppress proliferation of pathogenic CD4+ CD25- T cells when stimulated by their cognate antigens. Similarly, CD8+ Tregs significantly suppress EAE when transferred either pre-disease induction or during peak disease. The mechanism of disease inhibition depends, at least in part, on an antigen-specific, contact-dependent process and works through modulation of CD4+ T cell responses as well as antigen-presenting cells through a combination of cytotoxicity and cytokine-mediated modulation. This review provides an overview of our understanding of CD8+ T cells in immune-mediated disease, focusing particularly on our findings regarding regulatory CD8+ T cells both in MS and in EAE. Clinical relevance of these novel CD8-regulatory populations is discussed, providing insights into a potentially intriguing, novel therapeutic strategy for these diseases.

Original languageEnglish (US)
Pages (from-to)254-265
Number of pages12
JournalImmunologic Research
Volume59
Issue number1-3
DOIs
StatePublished - 2014

Fingerprint

Multiple Sclerosis
T-Lymphocytes
Autoimmune Experimental Encephalomyelitis
Pathology
Antigens
Viral Tumor Antigens
Immune System Diseases
Demyelinating Diseases
Antigen-Presenting Cells
Regulatory T-Lymphocytes
Population
Central Nervous System
Animal Models
Cytokines
Therapeutics

Keywords

  • Experimental autoimmune encephalomyelitis (EAE)
  • Glatiramer acetate (GA)
  • Immunoregulatory
  • Multiple sclerosis (MS)

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

Immune regulation of multiple sclerosis by CD8+ T cells. / Sinha, Sushmita; Itani, Farah R.; Karandikar, Nitin J.

In: Immunologic Research, Vol. 59, No. 1-3, 2014, p. 254-265.

Research output: Contribution to journalArticle

Sinha, S, Itani, FR & Karandikar, NJ 2014, 'Immune regulation of multiple sclerosis by CD8+ T cells', Immunologic Research, vol. 59, no. 1-3, pp. 254-265. https://doi.org/10.1007/s12026-014-8529-9
Sinha, Sushmita ; Itani, Farah R. ; Karandikar, Nitin J. / Immune regulation of multiple sclerosis by CD8+ T cells. In: Immunologic Research. 2014 ; Vol. 59, No. 1-3. pp. 254-265.
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