| Accelerated course of experimental autoimmune encephalomyelitis in PD-1-deficient central nervous system myelin mutants. | |
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MedLine Citation:
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PMID: 19443704 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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It is assumed that the onset and course of autoimmune inflammatory central nervous system (CNS) disorders (eg, multiple sclerosis) are influenced by factors that afflict immune regulation as well as CNS vulnerability. We challenged this concept experimentally by investigating how genetic alterations that affect myelin (primary oligodendrocyte damage in PLPtg mice) and/or T-cell regulation (deficiency of PD-1) influence both the onset and course of an experimental autoimmune CNS inflammatory disease [MOG(35-55)-induced experimental autoimmune encephalomyelitis (EAE)]. We observed that double pathology was associated with a significantly earlier onset of disease, a slight increase in the neurological score, an increase in the number of infiltrating cells, and enhanced axonal degeneration compared with wild-type mice and the respective, single mutant controls. Double-mutant PLPtg/PD-1(-/-) mice showed an increased production of interferon-gamma by CNS immune cells at the peak of disease. Neither PD-1 deficiency nor oligodendropathy led to detectable spread of antigenic MHC class I- or class II-restricted epitopes during EAE. However, absence of PD-1 clearly increased the propensity of T lymphocytes to expand, and the number of clonal expansions reliably reflected the severity of the EAE disease course. Our data show that the interplay between immune dysregulation and myelinopathy results in a stable exacerbation of actively induced autoimmune CNS inflammation, suggesting that the combination of several pathological issues contributes significantly to disease susceptibility or relapses in human disease. |
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Authors:
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Antje Kroner; Nicholas Schwab; Chi Wang Ip; Sonja Ortler; Kerstin Göbel; Klaus-Armin Nave; Mathias Mäurer; Rudolf Martini; Heinz Wiendl |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-05-14 |
Journal Detail:
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Title: The American journal of pathology Volume: 174 ISSN: 1525-2191 ISO Abbreviation: Am. J. Pathol. Publication Date: 2009 Jun |
Date Detail:
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Created Date: 2009-05-25 Completed Date: 2009-06-23 Revised Date: 2010-09-27 |
Medline Journal Info:
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Nlm Unique ID: 0370502 Medline TA: Am J Pathol Country: United States |
Other Details:
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Languages: eng Pagination: 2290-9 Citation Subset: AIM; IM |
Affiliation:
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Clinical Research Group for MS and Neuroimmunology, Department of Neurology, University of Wuerzburg, Josef Schneider Strasse 11, 97080 Wuerzburg, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antigens, Differentiation / genetics, immunology* Central Nervous System / immunology, pathology Encephalomyelitis, Autoimmune, Experimental / genetics, immunology*, pathology* Enzyme-Linked Immunosorbent Assay Immunohistochemistry Mice Mice, Knockout Mice, Transgenic Myelin Sheath / immunology*, pathology* Oligodendroglia / pathology T-Lymphocytes / immunology |
| Chemical | |
Reg. No./Substance:
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0/Antigens, Differentiation; 0/PD-1 antigen, mouse |
| Comments/Corrections | |
Erratum In:
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Am J Pathol. 2009 Sep;175(3):1349 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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