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Porcine CTLA4‐Ig prolong islet xenografts in rats by downregulating the direct pathway of T‐cell activation

2011; Wiley; Volume: 18; Issue: 1 Linguagem: Inglês

10.1111/j.1399-3089.2011.00627.x

1399-3089

Chao Zhai, Liang Yú, Haitao Zhu, Min Tian, Zhang Xiao-gang, Bo Wang,

Diabetes and associated disorders

Porcine pancreatic islets fused with pCTLA4-Ig were transplanted into diabetic rats. Xenografts survival was observed, and the underlying immunological rejection mechanisms were investigated.Control porcine islets, empty vector (Adv-GFP)-transfected, and gene-modified porcine islets were transplanted into the renal capsule of diabetic rats. The survival rates of the xenografts were observed. Changes in serum levels of IL-4 and γ-IFN in the recipients were assessed.The survival time of xenografts in the gene-modified porcine islets group was 34.50 ± 4.14 days, which was longer than those in the control group (34.50 ± 4.14 days vs. 7.43 ± 1.72 days and 7.22 ± 1.72 days; P < 0.01). Changes in the serum levels of IL-4 and γ-IFN between the groups of rats post-transplantation indicated the differentiation bias of T helper cells.The donor-originated pCTLA-IgG4 fusion protein inhibits the direct pathway of recipient T-cell priming, which might prolong xenograft survival.