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rdf:type |
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lifeskim:mentions |
umls-concept:C0025926,
umls-concept:C0026809,
umls-concept:C0030956,
umls-concept:C0039194,
umls-concept:C0085358,
umls-concept:C0205263,
umls-concept:C0567416,
umls-concept:C1332717,
umls-concept:C1413244,
umls-concept:C1416467,
umls-concept:C1418401,
umls-concept:C1513867,
umls-concept:C1706438,
umls-concept:C1998811,
umls-concept:C2698600
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pubmed:issue |
4
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pubmed:dateCreated |
2008-2-5
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pubmed:abstractText |
Systemic lupus erythematosus is an autoimmune disease caused primarily by autoantibodies (including IgG anti-DNA) and immune complexes that cause tissue damage. After tolerization with an artificial peptide (pConsensus, pCons) based on murine anti-DNA IgG sequences containing MHC class I and class II T cell determinants, lupus-prone (NZB x NZW)F(1) female (BWF(1)) mice develop regulatory CD4+CD25+ T cells and inhibitory CD8+ T cells, both of which suppress anti-DNA Ig production and immune glomerulonephritis. In the present work, we show that splenocytes from BWF(1) mice treated with pCons had significant expansion of primarily CD8+ T cells. CD4+ T cells and B cells were each directly suppressed by CD8+ T cells from tolerized mice in a contact-independent manner. Both pCons-induced CD8+CD28+ and CD8+CD28- T cells suppressed production of anti-DNA in vitro. Silencing with small interfering RNA of Foxp3 abrogated the suppression mediated by both CD8+ T cell subsets. Additionally, CD8+ T cells from tolerized mice were weakly cytotoxic against syngeneic B cells from old anti-DNA-producing mice, but not from young mice. Importantly, pCons treatment had dual effects on CD8+ suppressor T cells from tolerized mice, increasing the intracellular expression of Foxp3 while decreasing the surface expression of PD1 molecules. Blocking PD1/PDL1 interactions in the CD8+ T cells from tolerized mice reduced their expression of Foxp3 and their ability to suppress CD4+CD25- proliferation. In contrast, blocking PD1/PDL1 in naive T cells increased Foxp3 expression. Our data suggest that tolerization with pCons activates different subsets of inhibitory/cytotoxic CD8+ T cells whose targets are both CD4+CD25- effector T cells and B cells.
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pubmed:grant |
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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/Antibodies, Blocking,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Surface,
http://linkedlifedata.com/resource/pubmed/chemical/Apoptosis Regulatory Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Forkhead Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Foxp3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin G,
http://linkedlifedata.com/resource/pubmed/chemical/Pdcd1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Programmed Cell Death 1 Receptor
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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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 |
15
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pubmed:volume |
180
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2069-80
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:18250412-Amino Acid Sequence,
pubmed-meshheading:18250412-Animals,
pubmed-meshheading:18250412-Antibodies, Blocking,
pubmed-meshheading:18250412-Antigens, Surface,
pubmed-meshheading:18250412-Apoptosis Regulatory Proteins,
pubmed-meshheading:18250412-CD8-Positive T-Lymphocytes,
pubmed-meshheading:18250412-Cell Proliferation,
pubmed-meshheading:18250412-Consensus Sequence,
pubmed-meshheading:18250412-Crosses, Genetic,
pubmed-meshheading:18250412-Cytotoxicity, Immunologic,
pubmed-meshheading:18250412-Female,
pubmed-meshheading:18250412-Forkhead Transcription Factors,
pubmed-meshheading:18250412-Genetic Predisposition to Disease,
pubmed-meshheading:18250412-Immune Tolerance,
pubmed-meshheading:18250412-Immunoglobulin G,
pubmed-meshheading:18250412-Immunophenotyping,
pubmed-meshheading:18250412-Lupus Erythematosus, Systemic,
pubmed-meshheading:18250412-Lymphocyte Activation,
pubmed-meshheading:18250412-Mice,
pubmed-meshheading:18250412-Mice, Inbred BALB C,
pubmed-meshheading:18250412-Mice, Inbred NZB,
pubmed-meshheading:18250412-Molecular Sequence Data,
pubmed-meshheading:18250412-Peptides,
pubmed-meshheading:18250412-Programmed Cell Death 1 Receptor,
pubmed-meshheading:18250412-Spleen,
pubmed-meshheading:18250412-Up-Regulation
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pubmed:year |
2008
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pubmed:articleTitle |
pConsensus peptide induces tolerogenic CD8+ T cells in lupus-prone (NZB x NZW)F1 mice by differentially regulating Foxp3 and PD1 molecules.
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pubmed:affiliation |
Division of Rheumatology, Department of Medicine, David Geffen School of Medicine, University of California-Los Angeles, 1000 Veteran Avenue, Los Angeles, CA 90095, USA. rpsingh@mednet.ucla.edu
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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