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| Content Provider | PubMed Central |
|---|---|
| Author | Sinha, Sushmita Itani, Farah R. Karandikar, Nitin J. |
| 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 an 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 (APC) 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 about regulatory CD8+ T cells both in MS and EAE. Clinical relevance of these novel CD8-regulatory populations is discussed, providing insights into a potentially intriguing, novel therapeutic strategy for these diseases. |
| Related Links | http://dx.doi.org/10.1007/s12026-014-8529-9 |
| Ending Page | 265 |
| Page Count | 12 |
| Starting Page | 254 |
| File Format | |
| ISSN | 0257277X |
| e-ISSN | 15590755 |
| Journal | Immunologic research |
| Issue Number | 0 |
| Volume Number | 59 |
| Language | English |
| Publisher Date | 2014-08-01 |
| Access Restriction | Open |
| Subject Keyword | Immunology Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology |
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