Immunologic Research

, Volume 59, Issue 1, pp 254–265

Immune regulation of multiple sclerosis by CD8+ T cells

  • Sushmita Sinha
  • Farah R. Itani
  • Nitin J. Karandikar
IMMUNOLOGY AT THE UNIVERSITY OF IOWA

DOI: 10.1007/s12026-014-8529-9

Cite this article as:
Sinha, S., Itani, F.R. & Karandikar, N.J. Immunol Res (2014) 59: 254. doi:10.1007/s12026-014-8529-9

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.

Keywords

Multiple sclerosis (MS) CD8+ T cells Experimental autoimmune encephalomyelitis (EAE) Immunoregulatory Glatiramer acetate (GA) 

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Sushmita Sinha
    • 1
  • Farah R. Itani
    • 1
  • Nitin J. Karandikar
    • 1
  1. 1.The Interdisciplinary Graduate Program in Immunology, Department of PathologyUniversity of IowaIowa CityUSA