Document Detail


Accelerated course of experimental autoimmune encephalomyelitis in PD-1-deficient central nervous system myelin mutants.
MedLine Citation:
PMID:  19443704     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-05-14
Journal Detail:
Title:  The American journal of pathology     Volume:  174     ISSN:  1525-2191     ISO Abbreviation:  Am. J. Pathol.     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2009-05-25     Completed Date:  2009-06-23     Revised Date:  2014-03-10    
Medline Journal Info:
Nlm Unique ID:  0370502     Medline TA:  Am J Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2290-9     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
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:
0/Antigens, Differentiation; 0/Pdcd1 protein, mouse
Comments/Corrections
Erratum In:
Am J Pathol. 2009 Sep;175(3):1349

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