Document Detail

Down-regulation of myasthenogenic T cell responses by a dual altered peptide ligand via CD4+CD25+-regulated events leading to apoptosis.
MedLine Citation:
PMID:  15677327     Owner:  NLM     Status:  MEDLINE    
The myasthenogenic peptides p195-212 and p259-271 are sequences of the human acetylcholine receptor and were shown to induce myasthenia gravis-associated immune responses in mice. A dual altered peptide ligand (APL) composed of the two APLs of the myasthenogenic peptides inhibited, in vitro and in vivo, those responses. The aims of this study were to elucidate the events that follow the in vivo treatment with the dual APL and to characterize the cell population that is induced by the latter. We demonstrate here that s.c. administration of the dual APL up-regulates CD4+CD25+ regulatory T cells that are characterized by up-regulated expression of cytotoxic T lymphocyte-associated antigen 4, intracellular and membranal TGF-beta, and Foxp3. Administration of the dual APL to mice concomitant with the immunization with either of the myasthenogenic peptides resulted also in the up-regulation of c-Jun-NH2-terminal kinase activity and of Fas signaling pathway molecules as determined by measuring Fas, Fas ligand, and caspase 8. Thus, our results suggest that the suppression of myasthenia gravis-associated T cell responses exerted by the dual APL is mediated by the CD4+CD25+ immunoregulatory T cell function via TGF-beta or cytotoxic T lymphocyte-associated antigen 4, which further stimulate a cascade of events that up-regulates apoptosis.
Hava Ben-David; Michael Sela; Edna Mozes
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-01-26
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  102     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2005 Feb 
Date Detail:
Created Date:  2005-02-09     Completed Date:  2005-04-22     Revised Date:  2013-04-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2028-33     Citation Subset:  IM    
Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel.
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MeSH Terms
Antigens, CD4 / immunology*
Antigens, CD95 / metabolism
Apoptosis / physiology*
Biological Markers
Caspase 8
Caspases / metabolism
Cell Proliferation
Cells, Cultured
Interferon-gamma / immunology
JNK Mitogen-Activated Protein Kinases / metabolism
Lymph Nodes / cytology,  immunology
Mice, Inbred Strains
Myasthenia Gravis, Autoimmune, Experimental / immunology*
Peptides / genetics,  immunology*
Receptors, Interleukin-2 / immunology*
Signal Transduction / physiology
T-Lymphocytes / immunology*
Reg. No./Substance:
0/Antigens, CD4; 0/Antigens, CD95; 0/Biological Markers; 0/Ligands; 0/Peptides; 0/Receptors, Interleukin-2; 82115-62-6/Interferon-gamma; EC Mitogen-Activated Protein Kinases; EC 3.4.22.-/CASP8 protein, human; EC 3.4.22.-/Casp8 protein, mouse; EC 3.4.22.-/Caspase 8; EC 3.4.22.-/Caspases
Erratum In:
Proc Natl Acad Sci U S A. 2005 Aug 23;102(34):12288

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