Co-expression of sCD40LIg and CTLA4Ig mediated by adenovirus prolonged mouse skin allograft survival / 浙江大学学报(英文版)(B辑:生物医学和生物技术)
Journal of Zhejiang University. Science. B
;
(12): 436-444, 2006.
Artigo
em Inglês
| WPRIM
| ID: wpr-251904
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the role of simultaneous blockade of CD40/CD40L and B7/CD28 pathways in the immune tolerance via co-expression of sCD40LIg and CTLA4Ig mediated by replication-defective adenovirus.</p><p><b>METHODS</b>Ad-sCD40LIg-IRES(2)-CTLA4Ig, replication-defective adenovirus co-expressing sCD40LIg and CTLA4Ig, was constructed and identified. The co-expression of sCD40LIg and CTLA4Ig was evaluated with confocal laser scanning microscope and Western blotting. Skin transplantations of C57BL/6 to BALB/c mice were performed. PBS, Ad-Shuttle-CMV and Ad-sCD40LIg-IRES(2)-CTLA4Ig were administered. Skin graft survival was monitored and the mRNA expression of both genes was evaluated in the skin allografts.</p><p><b>RESULTS</b>Ad-sCD40LIg-IRES(2)-CTLA4Ig was constructed successfully and identified. The co-expression of sCD40LIg and CTLA4Ig was identified with confocal laser scanning microscopy and Western blotting. Compared to the skin graft mean survival time (MST) of non-treated group ((5.75+/-0.71) d) or Ad-Shuttle-CMV-treated group ((5.50+/-0.53) d), the skin graft MST was dramatically prolonged in the Ad-sCD40LIg-IRES(2)-CTLA4Ig-treated group ((16.38+/-1.19) d, P<0.001). The mRNA expression of both genes was detected.</p><p><b>CONCLUSION</b>Ad-sCD40LIg-IRES(2)-CTLA4Ig, a replication-defective adenovirus carrying genes encoding sCD40LIg and CTLA4Ig, was constructed. Simultaneous blockade of CD40/CD40L and B7/CD28 costimulatory pathway mediated by replication-defective adenovirus significantly prolonged skin allograft survival in mice.</p>
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Proteínas Recombinantes de Fusão
/
RNA Mensageiro
/
Transfecção
/
Adenoviridae
/
Transplante de Pele
/
Imunoconjugados
/
Reação em Cadeia da Polimerase Via Transcriptase Reversa
/
Efeito Citopatogênico Viral
/
Alergia e Imunologia
/
Abatacepte
Limite:
Animais
Idioma:
Inglês
Revista:
Journal of Zhejiang University. Science. B
Ano de publicação:
2006
Tipo de documento:
Artigo
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