Linked Life Data

19670423

Source:http://linkedlifedata.com/resource/pubmed/id/19670423

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2009-11-5
pubmed:abstractText
Although the role of CD4 T cells in tissue inflammation and organ injury resulting from ischemia and reperfusion injury (IRI) has been well documented, it remains unclear how CD4 T cells are activated and function in the absence of a specific antigen (Ag). We used a murine liver warm IRI model to determine first whether de novo Ag-specific CD4 T cell activation was required and then what its functional mechanism was. The critical role of CD4 T cells in liver immune activation against ischemia and reperfusion (IR) was confirmed in CD4 knockout mice and CD4 depleted wild-type mice. Interestingly, the inhibition of CD4 T cell activation without target cell depletion failed to protect livers against IRI, and this suggested that T cells function in liver IRI without Ag-specific de novo activation. To dissect the T cell functional mechanism, we found that CD154 blockade, but not interferon gamma (IFN-gamma) neutralization, inhibited local immune activation and protected livers from IRI. Furthermore, agonist anti-CD40 antibodies restored liver IRI in otherwise protected CD4-deficient hosts. Finally, fluorescence-activated cell sorting analysis of liver CD4 T cells revealed the selective infiltration of effector cells, which constitutively expressed a higher level of CD154 in comparison with their peripheral counterparts. IR triggered a significant liver increase in CD40 expression but not CD154 expression, and macrophages responded to toll-like receptor 4 and type I IFN stimulation to up-regulate CD40 expression. CONCLUSION: These novel findings provide evidence that CD4 T cells function in liver IRI via CD154 without de novo Ag-specific activation, and innate immunity-induced CD40 up-regulation may trigger the engagement of CD154-CD40 to facilitate tissue inflammation and injury.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1527-3350
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
50
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1537-46
pubmed:dateRevised
2010-12-3
pubmed:meshHeading
pubmed-meshheading:19670423-Animals, pubmed-meshheading:19670423-Antigens, CD4, pubmed-meshheading:19670423-Antigens, CD40, pubmed-meshheading:19670423-Antigens, CD8, pubmed-meshheading:19670423-CD4-Positive T-Lymphocytes, pubmed-meshheading:19670423-CD40 Ligand, pubmed-meshheading:19670423-Cells, Cultured, pubmed-meshheading:19670423-Disease Models, Animal, pubmed-meshheading:19670423-Hepatitis, pubmed-meshheading:19670423-Interferon-gamma, pubmed-meshheading:19670423-Liver, pubmed-meshheading:19670423-Male, pubmed-meshheading:19670423-Mice, pubmed-meshheading:19670423-Mice, Inbred C57BL, pubmed-meshheading:19670423-Mice, Knockout, pubmed-meshheading:19670423-Mice, Nude, pubmed-meshheading:19670423-Reperfusion Injury, pubmed-meshheading:19670423-Signal Transduction, pubmed-meshheading:19670423-Toll-Like Receptor 4
pubmed:year
2009
pubmed:articleTitle
CD4 T cells promote tissue inflammation via CD40 signaling without de novo activation in a murine model of liver ischemia/reperfusion injury.
pubmed:affiliation
Dumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural