Linked Life Data

11087143

Source:http://linkedlifedata.com/resource/pubmed/id/11087143

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2000-11-21
pubmed:abstractText
We have developed a model of transforming growth factor (TGF)beta1 gene transfer into mouse vascularized cardiac allografts to study the use of gene transfer as an immunosuppressive therapy in transplantation. Donor hearts were perfused with either DNA-liposome complexes or adenoviral vectors that encode the active form of human TGFbeta1. DNA-liposome mediated transfection prolonged allograft survival in approximately two-thirds of transplant recipients, while adenoviral delivery of TGFbeta1 was not protective. Protective TGFbeta1 gene transfer was associated with reduced Th1 responses and an inhibition of the alloantibody isotype switch. The protective effects of TGFbeta1 gene transfer were overridden by exogenous interleukin-12 administration. Interestingly, alloreactive CD4+ and CD8+ cells exhibited distinct sensitivities to TGFbeta1 gene transfer: CD4+ Th1 function was abrogated by this modality, although CD8+ Th1 function was not. Transient depletion of recipient CD8+ cells markedly prolonged the survival of grafts transfected with either DNA-liposome complexes or adenoviral vectors. Transgene expression persisted for at least 60 days, and Th1 responses were not detectable until CD8+ T cells repopulated the periphery. However, long-term transfected allografts appeared to exhibit exacerbated fibrosis and neointimal development. These manifestations of chronic rejection were absent in long-term transfected isografts, suggesting that long-term expression of active TGFbeta1 alone is not sufficient to induce fibrosis of the grafts. Collectively, these data illustrate the utility of immunosuppressive gene therapy as a treatment for transplantation when combined with additional conditioning regimens. Further, they illustrate that alloreactive CD4+ and CD8+ cells may be differentially influenced by cytokine manipulation strategies.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0041-1337
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
70
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1292-301
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11087143-Adenoviridae, pubmed-meshheading:11087143-Animals, pubmed-meshheading:11087143-CD4-Positive T-Lymphocytes, pubmed-meshheading:11087143-CD8-Positive T-Lymphocytes, pubmed-meshheading:11087143-Coronary Vessels, pubmed-meshheading:11087143-DNA, pubmed-meshheading:11087143-Female, pubmed-meshheading:11087143-Gene Expression, pubmed-meshheading:11087143-Gene Transfer, Horizontal, pubmed-meshheading:11087143-Heart Transplantation, pubmed-meshheading:11087143-Interleukin-12, pubmed-meshheading:11087143-Liposomes, pubmed-meshheading:11087143-Mice, pubmed-meshheading:11087143-Mice, Inbred BALB C, pubmed-meshheading:11087143-Mice, Inbred C57BL, pubmed-meshheading:11087143-Sensitivity and Specificity, pubmed-meshheading:11087143-Th1 Cells, pubmed-meshheading:11087143-Transforming Growth Factor beta, pubmed-meshheading:11087143-Transforming Growth Factor beta1, pubmed-meshheading:11087143-Transgenes
pubmed:year
2000
pubmed:articleTitle
DNA-liposome versus adenoviral mediated gene transfer of transforming growth factor beta1 in vascularized cardiac allografts: differential sensitivity of CD4+ and CD8+ T cells to transforming growth factor beta1.
pubmed:affiliation
Department of Surgery, University of Michigan School of Medicine, Ann Arbor 48109, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.