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猪 CTLA4-Ig 延长胰岛异种移植物在大鼠中的存活时间,通过下调 T 细胞激活的直接途径。

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

机构信息

Department of Hepatobiliary Surgery, First Affiliated Hospital, Medical College, Xi'an Jiaotong University, Xi'an, China.

出版信息

Xenotransplantation. 2011 Jan-Feb;18(1):40-5. doi: 10.1111/j.1399-3089.2011.00627.x.

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.

摘要

目的

将与 pCTLA4-Ig 融合的猪胰岛移植到糖尿病大鼠体内。观察异种移植物的存活情况,并研究其潜在的免疫排斥机制。

方法

将对照猪胰岛、空载体(Adv-GFP)转染和基因修饰的猪胰岛移植到糖尿病大鼠的肾包膜下。观察异种移植物的存活率。评估受体血清中白细胞介素 4(IL-4)和 γ-干扰素(IFN-γ)水平的变化。

结果

基因修饰的猪胰岛组异种移植物的存活时间为 34.50±4.14 天,明显长于对照组(34.50±4.14 天比 7.43±1.72 天和 7.22±1.72 天;P<0.01)。移植后大鼠血清中 IL-4 和 γ-IFN 水平的变化表明辅助性 T 细胞的分化偏向。

结论

供体来源的 pCTLA-IgG4 融合蛋白抑制了受体 T 细胞的初始直接途径,可能延长了异种移植物的存活时间。

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