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

Zhai C, Yu L, Zhu H, Tian M, Xiaogang Z, Bo W. Porcine CTLA4‐Ig prolong islet xenografts in rats by downregulating the direct pathway of T‐cell activation. Xenotransplantation 2011; 18: 40–45. © 2011 John Wiley & Sons A/S. Abstract: Aim: Porcine pancreatic islets fused with pCTLA4‐Ig were transplanted into diabetic rats. Xenografts survival was observed, and the underlying immunological rejection mechanisms were investigated. Methods: 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. Results: 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. Conclusions: The donor‐originated pCTLA‐IgG4 fusion protein inhibits the direct pathway of recipient T‐cell priming, which might prolong xenograft survival.