Induction of immune tolerance to a transplantation carbohydrate antigen by gene therapy with autologous lymphocytes transduced with adenovirus containing the corresponding glycosyltransferase gene.
Induction of immune tolerance to a transplantation carbohydrate antigen by gene therapy with autologous lymphocytes transduced with adenovirus containing the corresponding glycosyltransferase gene.
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通过用含有相应糖基转移酶基因的腺病毒转导的自体淋巴细胞进行基因治疗，诱导对移植糖抗原的免疫耐受。
DOI：
10.1038/sj.gt.3302178
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Galili,U
中科院分区：
文献类型：
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作者：
Ogawa,H;Yin,D-P;Galili,U
对移植糖抗原的耐受诱导在ABO血型不合的同种异体移植物或异种移植物的受者中具有临床意义。用于研究这种耐受性的实验动物模型是α1，3半乳糖基转移酶（α1，3GT）敲除（KO）小鼠，其缺乏α-gal表位（Galα1-3Galβ1-4GlcNAc-R），并能产生抗Gal抗体。相反，野生型（WT）小鼠合成α-gal表位并对其免疫耐受。3GT基因（AdαGT）表达α-gal表位。将此类淋巴细胞给予KO小鼠导致幼稚和记忆性抗Gal B细胞耐受。用表达多种α-gal表位的猪肾膜（PKM）免疫AdαGT转导的淋巴细胞耐受的小鼠后，不能产生抗-Gal。这种耐受性通过移植表达α-gal表位的同基因WT小鼠心脏得以延续。移植的WT心脏在耐受的KO小鼠中存活至少100天，尽管重复PKM免疫。对照小鼠接受了用缺乏α1，3GT基因的腺病毒转导的淋巴细胞，没有耐受性，但产生了抗Gal和排斥移植的WT心脏。这项研究表明，携带A或B转移酶基因的腺病毒转导的自体淋巴细胞可以诱导对人类血型抗原的类似耐受。
Induction of tolerance to transplantation carbohydrate antigens is of clinical significance in recipients of ABO-incompatible allografts, or of xenografts. The experimental animal model used for studying such tolerance was that of α1, 3galactosyltransferase (α1, 3GT) knockout (KO) mice, which lacks the α-gal epitope (Galα1-3Galβ1-4GlcNAc-R) and which can produce the anti-Gal antibody against it. In contrast, wild-type (WT) mice synthesize the α-gal epitope and are immunotolerant to it. KO lymphocytes transduced in vitro with adenovirus containing the α1, 3GT gene (AdαGT) express α-gal epitopes. Administration of such lymphocytes into KO mice resulted in tolerization of naïve and memory anti-Gal B cells. Mice tolerized by AdαGT transduced lymphocytes failed to produce anti-Gal following immunizations with pig kidney membranes (PKM) expressing multiple α-gal epitopes. This tolerance was perpetuated by transplanted syngeneic WT mouse hearts expressing α-gal epitopes. Transplanted WT hearts survived in the tolerized KO mice for at least 100 days, despite repeated PKM immunizations. Control mice receiving lymphocytes transduced with adenovirus lacking the α1, 3GT gene were not tolerized, but produced anti-Gal and rejected transplanted WT hearts. This study suggests that autologous lymphocytes transduced with adenovirus containing A or B transferase genes may induce a similar tolerance to blood group antigens in humans.