Fas ligand gene transfer prolongs rat renal allograft survival and down-regulates anti-apoptotic Bag-1 in parallel with enhanced Th2-type cytokine expression.
Transplantation
; 69(8): 1690-4, 2000 Apr 27.
Article
em En
| MEDLINE
| ID: mdl-10836382
ABSTRACT
BACKGROUND:
Fas ligand (FasL) induces apoptosis of cells bearing Fas receptor, and may play a role in the acquisition of immune privilege. We have previously shown that adenovirus (Ad)-mediated FasL gene transfer significantly prolongs survival in a strongly major histocompatibility complex-incompatible rat kidney allograft model. This study analyzes putative mechanisms of FasL-mediated effects, with particular emphasis on Th1 and Th2 immune activation and Bag-1 expression, a Bcl-2-binding anti-apoptotic protein.METHODS:
Kidney transplants were performed in Wistar-Furth to Lewis rat combination. Donor kidneys were perfused in situ with Ad-FasL or Ad-beta-Gal, and then transplanted. Kidney allografts were harvested at days 2, 7, and 56 and were evaluated by hematoxylin and eosin and immunohistochemical staining. The expression of FasL, Bag-1, and Th1/Th2 cytokine genes was assessed by Northern blots, Western blots, and competitive template reverse-transcriptase polymerase chain reaction, respectively.RESULTS:
Intragraft expression of FasL was enhanced, whereas that of anti-apoptotic Bag-1 gene was diminished throughout, in Ad-FasL-transduced well-functioning renal allografts, compared with Ad-beta-Gal-treated rejecting controls. In parallel, the expression of mRNA coding for IL-2 and IFN-gamma remained depressed, whereas that of IL-4 and IL-10 reciprocally and progressively increased in the Ad-FasL animal group.CONCLUSIONS:
Prolonged survival in Ad-FasL-transduced rat renal allograft model correlates with down-regulation of Bag-1, a novel anti-apoptotic gene, and preferential Th2-type cytokine elaboration profile at the graft site. Because Th1-like cells are sensitive to FasL-mediated cytotoxic effects, T-cell apoptosis may preferentially spare Th2-like cells, with resultant prolonged graft survival.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Glicoproteínas de Membrana
/
Proteínas de Transporte
/
Citocinas
/
Transplante de Rim
/
Técnicas de Transferência de Genes
/
Células Th2
/
Sobrevivência de Enxerto
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Transplantation
Ano de publicação:
2000
Tipo de documento:
Article
País de afiliação:
Estados Unidos