rdf:type |
|
lifeskim:mentions |
|
pubmed:issue |
5
|
pubmed:dateCreated |
1995-4-13
|
pubmed:abstractText |
The use of E1-deleted recombinant adenoviruses in gene therapy has consistently been associated with transient gene expression and inflammation due to immune-based destruction of the infected cells. We have used murine models of adenovirus-mediated gene transfer to liver to investigate these immunologic mechanisms. Adoptive transfer experiments, as well as studies involving genetic knockout mice, confirmed the original hypothesis that cell-mediated immunity induced by E1-deleted adenovirus destroyed trans-gene-expressing hepatocytes and defined MHC class I-restricted CD8+ cytolytic lymphocytes as the primary immune effectors for hepatocyte destruction. Responses mediated by CD4+ cells per se were insufficient to mediate destruction of hepatocytes in vivo, despite the activation of virus-specific T helper cells of Th1 subsets. A better understanding of the response of the host to in vivo gene therapy is important in evaluating its usefulness in humans.
|
pubmed:language |
eng
|
pubmed:journal |
|
pubmed:citationSubset |
IM
|
pubmed:chemical |
|
pubmed:status |
MEDLINE
|
pubmed:month |
Aug
|
pubmed:issn |
1074-7613
|
pubmed:author |
|
pubmed:issnType |
Print
|
pubmed:volume |
1
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
433-42
|
pubmed:dateRevised |
2006-11-15
|
pubmed:meshHeading |
pubmed-meshheading:7533647-Adenoviridae Infections,
pubmed-meshheading:7533647-Adenovirus E1 Proteins,
pubmed-meshheading:7533647-Animals,
pubmed-meshheading:7533647-Antigens, Viral,
pubmed-meshheading:7533647-CD4-Positive T-Lymphocytes,
pubmed-meshheading:7533647-CD8-Positive T-Lymphocytes,
pubmed-meshheading:7533647-Epitopes,
pubmed-meshheading:7533647-Gene Transfer Techniques,
pubmed-meshheading:7533647-Histocompatibility Antigens Class I,
pubmed-meshheading:7533647-Histocompatibility Antigens Class II,
pubmed-meshheading:7533647-Liver,
pubmed-meshheading:7533647-Mice,
pubmed-meshheading:7533647-Mice, Inbred C57BL,
pubmed-meshheading:7533647-Recombinant Proteins,
pubmed-meshheading:7533647-Spleen,
pubmed-meshheading:7533647-T-Lymphocyte Subsets,
pubmed-meshheading:7533647-T-Lymphocytes, Cytotoxic,
pubmed-meshheading:7533647-T-Lymphocytes, Helper-Inducer
|
pubmed:year |
1994
|
pubmed:articleTitle |
MHC class I-restricted cytotoxic T lymphocytes to viral antigens destroy hepatocytes in mice infected with E1-deleted recombinant adenoviruses.
|
pubmed:affiliation |
Department of Molecular and Cellular Engineering, University of Pennsylvania Medical Center, Philadelphia.
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|