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rdf:type |
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lifeskim:mentions |
umls-concept:C0007589,
umls-concept:C0013081,
umls-concept:C0041904,
umls-concept:C0111208,
umls-concept:C0162493,
umls-concept:C0167627,
umls-concept:C0205191,
umls-concept:C0332206,
umls-concept:C0752087,
umls-concept:C1423842,
umls-concept:C1511938
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pubmed:issue |
11
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pubmed:dateCreated |
2001-5-21
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pubmed:abstractText |
Myasthenia gravis (MG) and experimental autoimmune MG (EAMG) are T cell-dependent Ab-mediated autoimmune disorders, in which the nicotinic acetylcholine receptor (AChR) is the major autoantigen. Th1-type cells and costimulatory factors such as CD40 ligand (CD40L) contribute to disease pathogenesis by producing proinflammatory cytokines and by activating autoreactive B cells. In this study we demonstrate the capacity of CD40L blockade to modulate EAMG, and analyze the mechanism underlying this disease suppression. Anti-CD40L Abs given to rats at the chronic stage of EAMG suppress the clinical progression of the autoimmune process and lead to a decrease in the AChR-specific humoral response and delayed-type hypersensitivity. The cytokine profile of treated rats suggests that the underlying mechanism involves down-regulation of AChR-specific Th1-regulated responses with no significant effect on Th2- and Th3-regulated AChR-specific responses. EAMG suppression is also accompanied by a significant up-regulation of CTLA-4, whereas a series of costimulatory factors remain unchanged. Adoptive transfer of splenocytes from anti-CD40L-treated rats does not protect recipient rats against subsequently induced EAMG. Thus it seems that the suppressed progression of chronic EAMG by anti-CD40L treatment does not induce a switch from Th1 to Th2/Th3 regulation of the AChR-specific immune response and does not induce generation of regulatory cells. The ability of anti-CD40L treatment to suppress ongoing chronic EAMG suggests that blockade of CD40L may serve as a potential approach for the immunotherapy of MG and other Ab-mediated autoimmune diseases.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Differentiation,
http://linkedlifedata.com/resource/pubmed/chemical/CD40 Ligand,
http://linkedlifedata.com/resource/pubmed/chemical/CTLA-4 Antigen,
http://linkedlifedata.com/resource/pubmed/chemical/CTLA4 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/Immune Sera,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoconjugates,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin G,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin Isotypes,
http://linkedlifedata.com/resource/pubmed/chemical/Immunosuppressive Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cholinergic,
http://linkedlifedata.com/resource/pubmed/chemical/abatacept
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0022-1767
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
166
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6893-8
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:11359850-Animals,
pubmed-meshheading:11359850-Antibody Specificity,
pubmed-meshheading:11359850-Antigens, CD,
pubmed-meshheading:11359850-Antigens, Differentiation,
pubmed-meshheading:11359850-B-Lymphocytes,
pubmed-meshheading:11359850-CD40 Ligand,
pubmed-meshheading:11359850-CTLA-4 Antigen,
pubmed-meshheading:11359850-Cell Differentiation,
pubmed-meshheading:11359850-Cells, Cultured,
pubmed-meshheading:11359850-Chronic Disease,
pubmed-meshheading:11359850-Cytokines,
pubmed-meshheading:11359850-Down-Regulation,
pubmed-meshheading:11359850-Female,
pubmed-meshheading:11359850-Humans,
pubmed-meshheading:11359850-Hypersensitivity, Delayed,
pubmed-meshheading:11359850-Immune Sera,
pubmed-meshheading:11359850-Immunoconjugates,
pubmed-meshheading:11359850-Immunoglobulin G,
pubmed-meshheading:11359850-Immunoglobulin Isotypes,
pubmed-meshheading:11359850-Immunosuppressive Agents,
pubmed-meshheading:11359850-Injections, Intraperitoneal,
pubmed-meshheading:11359850-Injections, Subcutaneous,
pubmed-meshheading:11359850-Lymphocyte Activation,
pubmed-meshheading:11359850-Myasthenia Gravis, Autoimmune, Experimental,
pubmed-meshheading:11359850-Rats,
pubmed-meshheading:11359850-Rats, Inbred Lew,
pubmed-meshheading:11359850-Receptors, Cholinergic,
pubmed-meshheading:11359850-Th1 Cells,
pubmed-meshheading:11359850-Th2 Cells,
pubmed-meshheading:11359850-Torpedo,
pubmed-meshheading:11359850-Up-Regulation
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pubmed:year |
2001
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pubmed:articleTitle |
Blockade of CD40 ligand suppresses chronic experimental myasthenia gravis by down-regulation of Th1 differentiation and up-regulation of CTLA-4.
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pubmed:affiliation |
Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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