Journal article
CD4(+) T-lymphocytes mediate ischemia/reperfusion-induced inflammatory responses in mouse liver
The Journal of clinical investigation, Vol.100(2), pp.279-289
07/15/1997
DOI: 10.1172/JCI119533
PMCID: PMC508190
PMID: 9218504
Abstract
The success of orthotopic liver transplantation is dependent on multiple factors including MHC tissue compatibility and ischemic/reperfusion injury. Ischemic/reperfusion (I/R) injury in the liver occurs in a biphasic pattern consisting of both acute phase (oxygen free radical mediated) and subacute phase (neutrophil-mediated) damage. Although numerous studies have given insights into the process of neutrophil recruitment after I/R injury to the liver, the exact mechanism that initiates this subacute response remains undefined. Using a T cell-deficient mouse model, we present data that suggests that T-lymphocytes are key mediators of subacute neutrophil inflammatory responses in the liver after ischemia and reperfusion. To this end, using a partial lobar liver ischemia model, we compared the extent of reperfusion injury between immune competent BALB/c and athymic nu/nu mice. Studies evaluating the extent of liver damage as measured by serum transaminases (GPT) demonstrate similar acute (3-6 h) post-I/R responses in these two mouse models. In contrast, the subacute phase (16-20 h) of liver injury, as measured by both serum GPT levels and percent hepatocellular necrosis, was dramatically reduced in T cell-deficient mice as compared with those with an intact immune system. This reduction in liver injury seen in nu/nu mice was associated with a 10-fold reduction in hepatic neutrophil infiltration. Adoptive transfer of T cell-enriched splenocytes from immune competent mice was capable of reconstituting the neutrophil-mediated subacute inflammatory response within T cell-deficient nu/nu mice. Furthermore, in vivo antibody depletion of CD4(+) T-lymphocytes in immune competent mice resulted in a reduction of subacute phase injury and inflammation as measured by serum GPT levels and neutrophil infiltration. In contrast, depletion of CD8(+) T-lymphocytes had no effect on these indexes of subacute inflammation. Kinetic analysis of T cell infiltration in the livers of BALB/c mice demonstrated a fivefold increase in the number of hepatic CD4(+) T-lymphocytes within the first hour of reperfusion with no significant change in the number of CD8(+) T-lymphocytes. In summary, these results implicate CD4(+) T-lymphocytes as key regulators in initiating I/R-induced inflammatory responses in the liver. Such findings have implications for therapy directed at the early events in this inflammatory cascade that may prove useful in liver transplantation.
Details
- Title: Subtitle
- CD4(+) T-lymphocytes mediate ischemia/reperfusion-induced inflammatory responses in mouse liver
- Creators
- R M Zwacka - University of PennsylvaniaY Zhang - University of PennsylvaniaJ Halldorson - University of PennsylvaniaH Schlossberg - University of PennsylvaniaL Dudus - University of PennsylvaniaJ F Engelhardt - University of Pennsylvania
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.100(2), pp.279-289
- DOI
- 10.1172/JCI119533
- PMID
- 9218504
- PMCID
- PMC508190
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Language
- English
- Date published
- 07/15/1997
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Anatomy and Cell Biology; Radiation Oncology; Internal Medicine
- Record Identifier
- 9984284355002771
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