CTLA4-Ig-modified dendritic cells inhibit lymphocyte-mediated alloimmune responses and prolong the islet graft survival in mice
CTLA4-Ig-modified dendritic cells inhibit lymphocyte-mediated alloimmune responses and prolong the islet graft survival in mice
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CTLA4-Ig 修饰的树突状细胞可抑制淋巴细胞介导的同种免疫反应，并延长小鼠胰岛移植物的存活时间。
DOI：
10.1016/j.trim.2008.05.005
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发表时间：
2008-07-01
影响因子：
1.5
通讯作者：
Shen, Guan-Xin
中科院分区：
文献类型：
--
作者：
Yang, Dao-Feng;Qiu, Wen-Hong;Shen, Guan-Xin
抗原特异性耐受的诱导是预防和治疗同种异体移植排斥反应的关键。本研究将CTLA4-Ig基因转染到树突状细胞（dc）中，研究其对体外抑制淋巴细胞活性和诱导小鼠胰岛移植免疫耐受的作用。以链脲佐菌素诱导的IDDM C57BL/6小鼠为模型小鼠。将BALB/c小鼠分离的胰岛细胞移植到模型小鼠的肾胶囊中，并注射CTLA4-Ig修饰的dc （mDCs）。结果表明，mDCs能显著抑制T淋巴细胞增殖，诱导T淋巴细胞凋亡；而未经修饰的树突状细胞（umDCs）则能促进小鼠淋巴细胞的增殖。与注射umdc和IgG1修饰dc相比，注射mDCs延长了IDDM小鼠的同种异体移植存活时间，并在3天内使其血浆葡萄糖（PG）水平正常化，并维持超过2周。与对照组相比，mDCs处理的受体小鼠ifn - γ水平较低，IL-4水平较高，提示mDCs导致Th1/Th2偏离。胰岛移植7天后，肾标本HE染色显示mDCs处理小鼠的胰岛和肾脏结构完整，胰岛细胞数量增加。我们的研究表明，表达CTLA4-Ig融合蛋白的树突状细胞可以通过抑制异体小鼠T细胞增殖，诱导对胰岛移植物的免疫耐受，延长同种异体移植物的存活时间。(C) 2008年Elsevier B.V.出版
The induction of antigen specific tolerance is critical for prevention and treatment of allograft rejection. In this study, we transfected CTLA4-Ig gene into dendritic cells (DCs), and investigated their effect on inhibition of lymphocyte activity in vitro and induction of immune tolerance on pancreatic islet allograft in mice. An IDDM C57BL/6 murine model induced by streptozotocin is as model mouse. The model mice were transplanted of the islet cells isolated from the BALB/c mice to their kidney capsules, and injected of CTLA4-Ig modified DCs (mDCs). The results showed that mDCs could significantly inhibit T lymphocyte proliferation and induce its apoptosis; whereas, unmodified DCs (umDCs) promoted the murine lymphocyte proliferation. Compared with injection of umDCs and IgG1 modified DCs, the injection of mDCs prolonged IDDM mice's allograft survival, and normalized their plasma glucose (PG) levels within 3 days and maintained over 2 weeks. The level of IFN-gamma was lower and the level of IL-4 was higher in mDCs treated recipient mice than that in control mice, it indicated that mDCs led to Th1/Th2 deviation. After 7 days of islet transplantation, HE stain of the renal specimens showed that the islets and kidneys were intact in structure, and islet cells numbers are increased in mDCs treated mice. Our studies suggest that DCs expressing CTLA4-Ig fusion protein can induce the immune tolerance to islet graft and prolong the allograft survival through the inhibition of T cell proliferation in allogeneic mice. (C) 2008 Published by Elsevier B.V.