NDLI: A dual altered peptide ligand down-regulates myasthenogenic T cell responses by up-regulating CD25- and CTLA-4-expressing CD4+ T cells.

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A dual altered peptide ligand down-regulates myasthenogenic T cell responses by up-regulating CD25- and CTLA-4-expressing CD4+ T cells.

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A dual altered peptide ligand down-regulates myasthenogenic T cell responses by up-regulating CD25- and CTLA-4-expressing CD4+ T cells.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Paas-rozner, Miri Sela, Michael Mozes, Edna
Description	Author Affiliation: Paas-Rozner M ( Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel.);
Abstract	Immunization of mice with two myasthenogenic peptides, p195-212 and p259-271, which are sequences of the human acetylcholine receptor, resulted in myasthenia gravis (MG)-associated immune responses. 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 further elucidate the mechanism/s by which the dual APL down-regulates MG-associated responses in vivo and characterize the cell population/s involved in this immunomodulatory suppressive effect. We have shown here that s.c. administration of the dual APL activates CD4CD25-expressing cells in lymph nodes (LN) of SJL mice. Furthermore, depletion of these cells diminished significantly the inhibitory effect of the APL on p195-212-specific proliferative responses. Depletion of the CD4+CD25+ cells was accompanied with a decrease in the secretion of the immunosuppressive cytokine, transforming growth factor (TGF)-beta. Administration of the dual APL resulted also in the up-regulation of the expression of cytotoxic T lymphocyte antigen (CTLA)-4 and in a down-regulated expression of CD28 on LN cells. Blockade of the CTLA-4 function, in vitro, abrogated the inhibitory effect of the dual APL on the proliferative responses specific to p195-212. Thus, our results suggest that the active suppression exerted by the dual APL is mediated by the CD4+CD25+ immunoregulatory cell population, either directly through the CTLA-4 molecule expressed on these cells, and/or indirectly by causing the differentiation of other regulatory T cell population/s that secrete immunosuppressive cytokines.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	11
Volume Number	100
Language	English
Publisher	National Academy of Sciences
Publisher Date	2003-05-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Antigens, Differentiation Immunology CD4-Positive T-Lymphocytes Down-Regulation Immunoconjugates Myasthenia Gravis Receptors, Interleukin-2 T-Lymphocytes Up-Regulation Abatacept Amino Acid Sequence Animals Antibodies Antigens, CD CTLA-4 Antigen Lymphocyte Depletion Mice Mice, Inbred Strains Molecular Sequence Data Research Support, Non-U.S. Gov't Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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