Linked Life Data

19249545

Source:http://linkedlifedata.com/resource/pubmed/id/19249545

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2009-3-2
pubmed:abstractText
Cell-mediated immunity, especially of human CD8+ cytotoxic T lymphocytes (CTLs) is believed to have an important role in the long-term survival of pig islet xenografts. Protection against human CD8+ CTL cytotoxicity may reduce the direct damage to pig islets and enable long-term xenograft survival in pig-to-human islet xenotransplantation. We have previously reported that c-FLIP(S/L) genes, which are potent inhibitors of death receptor-mediated proapoptotic signals through binding competition with caspase-8 for recruitment to the Fas-associated via death domain (FADD), markedly suppress human CD8+ CTL-mediated xenocytotoxicity. In addition, the cytoprotective effects of c-FLIP(L) seem to be significantly stronger than those of c-FLIP(S). Accordingly, in the present study, expression of c-FLIP(L) was induced in intact pig islets by adenoviral transduction. Consequently, the cytoprotective capacity of the transgene in pig islets was examined in in vitro and in vivo exposure to human CD8+ CTLs. Cells from untransduced islets or mock islets were sensitive to CD8+ CTL-mediated lysis (59.3% +/- 15.9% and 64.0% +/- 8.9% cytotoxicity, respectively). In contrast, cells from pig islets transduced with the c-FLIP(L) gene were markedly protected from lysis (30.5% +/- 3.5%). Furthermore, prolonged xenograft survival was elicited from pig islets transduced with this molecule as assessed using an islet transplant model using the rat kidney capsule. Thus, these data indicate that intact pig islets can be transduced to express c-FLIP(L) with adenovirus. Pig islets expressing c-FLIP(L) are significantly resistant to human CTL killing and further exhibit beneficial effects to prolong xenograft survival.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0041-1345
pubmed:author
pubmed:issnType
Print
pubmed:volume
41
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
319-22
pubmed:meshHeading
pubmed:articleTitle
Adenovirus-mediated gene expression of the human c-FLIP(L) gene protects pig islets against human CD8(+) cytotoxic T lymphocyte-mediated cytotoxicity.
pubmed:affiliation
Department of Surgery, Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, Japan. mtanemura@gesurg.med.osaka-u.ac.jp
pubmed:publicationType
Journal Article