Journal article
Immune regulation of multiple sclerosis by CD8+ T cells
Immunologic research, Vol.59(1), pp.254-265
08/2014
DOI: 10.1007/s12026-014-8529-9
PMCID: PMC4125494
PMID: 24845461
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.
Details
- Title: Subtitle
- Immune regulation of multiple sclerosis by CD8+ T cells
- Creators
- Sushmita Sinha - University of IowaFarah Itani - University of IowaNitin Karandikar - University of Iowa
- Contributors
- Gail A Bishop (Editor)
- Resource Type
- Journal article
- Publication Details
- Immunologic research, Vol.59(1), pp.254-265
- DOI
- 10.1007/s12026-014-8529-9
- PMID
- 24845461
- PMCID
- PMC4125494
- NLM abbreviation
- Immunol Res
- ISSN
- 0257-277X
- eISSN
- 1559-0755
- Publisher
- Springer US
- Language
- English
- Date published
- 08/2014
- Academic Unit
- Microbiology and Immunology; President; Pathology; Fraternal Order of Eagles Diabetes Research Center
- Record Identifier
- 9984186518602771
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