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ZJUS-B
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology)  2006, Vol. 7 Issue (6): 436-444    DOI: 10.1631/jzus.2006.B0436
Biomedicine     
Co-expression of sCD40LIg and CTLA4Ig mediated by adenovirus prolonged mouse skin allograft survival
LI Zhao-lun, TIAN Pu-xun, XUE Wu-jun, WU Jun
Department of Renal Transplantation, the First Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an 710061, China; Institute of Burn Research, Southwest Hospital, the Third Military Medical University, Chongqing 400038, China
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Abstract  Objective: 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. Methods: Ad-sCD40LIg-IRES2-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-IRES2-CTLA4Ig were administered. Skin graft survival was monitored and the mRNA expression of both genes was evaluated in the skin allografts. Results: Ad-sCD40LIg-IRES2-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-IRES2-CTLA4Ig-treated group ((16.38±1.19) d, P<0.001). The mRNA expression of both genes was detected. Conclusion: Ad-sCD40LIg-IRES2-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.

Key words： Immune tolerance      CTLA4Ig      sCD40LIg      Replication-defective recombinant adenovirus      Skin graft     
Received: 26 October 2005     
CLC:  R392.11  
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LI Zhao-lun
TIAN Pu-xun
XUE Wu-jun
WU Jun
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LI Zhao-lun, TIAN Pu-xun, XUE Wu-jun, WU Jun. Co-expression of sCD40LIg and CTLA4Ig mediated by adenovirus prolonged mouse skin allograft survival. Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2006, 7(6): 436-444.

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http://www.zjujournals.com/xueshu/zjus-b/10.1631/jzus.2006.B0436     OR     http://www.zjujournals.com/xueshu/zjus-b/Y2006/V7/I6/436

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