Linked Life Data

12841875

Source:http://linkedlifedata.com/resource/pubmed/id/12841875

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2003-7-4
pubmed:abstractText
Allogeneic bone marrow transplantation and donor lymphocyte infusion are powerful treatments for chemotherapy-resistant leukemia. Tumor eradication is attributed to a graft-versus-leukemia reaction by the donor-derived cytotoxic T lymphocytes (CTLs), but the same cell population may cause severe graft-versus-host disease. One strategy to suppress harmful CTL activity is to incorporate a suicide gene into the donor lymphocytes prior to infusion, and to destroy these cells when they aggressively attack nonmalignant host tissues. In this study, we investigated the feasibility of using a Fas-estrogen receptor fusion protein (MfasER) to control T cell-mediated cytotoxicity, based on our previous finding that the chimera transmits a Fas-mediated death signal through activation by estrogen binding. A murine CTL line CTLL-2 was transfected with a vector encoding MfasER, and the growth, viability and cytotoxic activity of the transfected cells (CTLL/MfasER) were analyzed. The expression of apoptosis-related proteins such as Fas ligand and perforin was also investigated. In the absence of estrogen, CTLL/MfasER showed similar growth to parental CTLL-2, and the killing activity was preserved. Addition of 10 (-7) M estrogen induced a rapid apoptosis of CTLL/MfasER, and the cytotoxicity was severely impaired. A decrease of Fas ligand and perforin in the estrogen-treated CTLL/MfasER was seen in an immunoblot analysis. These functional and biochemical analyses showed that the estrogen-inducible apoptosis in MfasER-expressing CTLs rapidly terminated their target cell killing. The feasibility of using the MfasER-estrogen system to control graft-versus-host disease was demonstrated.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1347-9032
pubmed:author
pubmed:issnType
Print
pubmed:volume
94
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
639-43
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Reduction of CTLL-2 cytotoxicity by induction of apoptosis with a Fas-estrogen receptor chimera.
pubmed:affiliation
Division of Genetic Therapeutics, Center for Molecular Medicine, Jichi Medical School, Tochigi 329-0498, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't