Linked Life Data

20883163

Source:http://linkedlifedata.com/resource/pubmed/id/20883163

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2010-10-4
pubmed:abstractText
Chronic hepatitis C virus (HCV) infection is associated with T-cell exhaustion that is mediated through upregulation of the PD-1 negative regulatory pathway. PD-1 expression is induced by HCV core protein, which also induces upregulation of SOCS-1, a key modulator that controls the Jak/STAT pathway regulating cytokine expression. To determine whether these two negative regulatory pathways are linked during T-cell signaling, SOCS-1 expression was examined by blocking the PD-1 pathway in T cells stimulated with anti-CD3/CD28 in the presence of HCV core protein. T cells isolated from healthy subjects or HCV-infected individuals were treated with anti-PD-1 or anti-PDL-1 antibodies in the presence or absence of HCV core protein, and SOCS-1 gene expression was detected by RT-PCR or immunoblotting, while T-cell functions were assayed by flow cytometric analyses. Both PD-1 and SOCS-1 gene expression were upregulated in healthy T cells exposed to HCV core protein, and blocking the PD-1 pathway downregulated SOCS-1 gene expression in these cells. Additionally, T cells isolated from chronically HCV-infected subjects exhibited increased PD-1 and SOCS-1 expression compared to healthy subjects, and SOCS-1 expression in T cells isolated from HCV-infected subjects was also inhibited by blocking PD-1 signaling; this in turn enhanced the phosphorylation of STAT-1, and improved the impaired T-cell proliferation observed in the setting of HCV infection. These data demonstrate that PD-1 and SOCS-1 are linked in dysregulating T-cell signaling during HCV infection, and their cross-talk may coordinately inhibit T-cell signaling pathways that lead to T-cell exhaustion during chronic viral infection.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1557-8976
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
487-95
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:20883163-Antigens, CD, pubmed-meshheading:20883163-Apoptosis Regulatory Proteins, pubmed-meshheading:20883163-Cells, Cultured, pubmed-meshheading:20883163-Flow Cytometry, pubmed-meshheading:20883163-Gene Expression Profiling, pubmed-meshheading:20883163-Hepacivirus, pubmed-meshheading:20883163-Hepatitis C, Chronic, pubmed-meshheading:20883163-Humans, pubmed-meshheading:20883163-Immunoblotting, pubmed-meshheading:20883163-Programmed Cell Death 1 Receptor, pubmed-meshheading:20883163-RNA, Messenger, pubmed-meshheading:20883163-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:20883163-Signal Transduction, pubmed-meshheading:20883163-Suppressor of Cytokine Signaling Proteins, pubmed-meshheading:20883163-T-Lymphocytes, pubmed-meshheading:20883163-Viral Core Proteins
pubmed:year
2010
pubmed:articleTitle
Programmed death-1 affects suppressor of cytokine signaling-1 expression in T cells during hepatitis C infection.
pubmed:affiliation
Medical Service, Department of Veterans Affairs, James H. Quillen Veterans Administration Medical Center, Mountain Home, Tennessee, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural