THE USE OF DIRECT ULTRAVIOLET IRRADIATION AND CYCLOSPORINE IN FACILITATING INDEFINITE PANCREATIC ISLET ALLOGRAFT ACCEPTANCE
THE USE OF DIRECT ULTRAVIOLET IRRADIATION AND CYCLOSPORINE IN FACILITATING INDEFINITE PANCREATIC ISLET ALLOGRAFT ACCEPTANCE
复制标题
使用直接紫外线照射和环孢菌素促进无限期胰岛同种异体移植物的接受
DOI：
10.1097/00007890-198412000-00002
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发表时间：
1984
期刊：
影响因子：
6.2
通讯作者：
M. Hardy
中科院分区：
文献类型：
--
作者：
H. Lau;K. Reemtsma;M. Hardy
我们以前已经表明，直接紫外线（UV）照射胰岛可以降低其免疫原性，而不改变其内分泌功能，并延长存活期的胰岛同种异体移植物在刘易斯到ACI株组合，而不使用免疫抑制。本研究将这项工作扩展到研究UV照射的Wistar-Furth胰岛的存活率，即reptozotocin-糖尿病刘易斯大鼠，在这种情况下，受体对W/F同种异体抗原具有相对“高应答”。刘易斯受者在移植后1周内接受24小时培养的W/F胰岛，均出现同种异体胰岛移植排斥反应，而在移植后0、+1和+2天给予15或30 mg/kg环孢素（CsA）免疫抑制，对延长胰岛移植物存活时间无效。Wistar-Furth胰岛在移植前以850-900 J/m2进行UV照射并培养24小时，其存活时间并不比接受未处理胰岛的对照动物中的胰岛长（MST 5.5 ± 1天）。当胰岛的UV照射与受体移植物周围用CsA（15 mg/kg）在0、+1和+2天处理相结合时，胰岛移植物存活显著延长（MST为18 ± 4.1天）。在相同的移植围手术期（0，+1，+2天），用增加剂量的CsA（30 mg/kg）治疗接受UV照射胰岛的糖尿病受者，导致100%的胰岛移植物存活超过120天。这些数据表明，在“高反应”受体中，使用移植前紫外线照射胰岛同种异体移植物和CsA对受体进行围移植免疫抑制诱导胰岛同种异体移植物存活时间延长的有效性和协同作用，其中单独使用任一种方式可能无效。
We have previously shown that direct ultraviolet (UV) irradiation of islets can reduce their immunogenicity without alteration of their endocrine function and effect prolonged survival of islet allografts in the Lewis-to-ACI strain combination without the use of immuno-suppression. This study extends that work to investigate the survival of UV-irradiated Wistar-Furth islets instreptozotocin-diabetic Lewis rats, in which case the recipient is a relatively “high responder” to W/F alloantigens. Lewis recipients of 24-hr cultured W/F isletsuniformly rejected islet allografts within one week of transplantation while the additional immunosuppression with cyclosporine (CsA) at 15 or 30 mg/kg on days 0, +1, and +2 was ineffective in prolonging islet allograft survival. Wistar-Furth islets, which were UV-irradiated at 850–900 J/m2 and cultured for 24 hr prior to transplantation, did not survive any longer than those in control animals receiving untreated islets (MST 5.5 ± 1 day). When UV irradiation of islets was combined with recipient peritransplant treatment with CsA at 15 mg/kg on days 0, +1, and +2 islet allograft survival was markedly prolonged (MST of 18 ± 4.1 days). Treatment of diabetic recipients of UV irradiated islets with an increased dose of CsA (30 mg/kg) during the same peritransplant period (0, +1, +2 days) resulted in 100% islet allograft survival beyond 120 days. This data demonstrate the effectiveness and synergism between the use of the pretransplant UV irradiation of islet allograft and the peritransplant immunosuppression of the recipient with CsA in inducing prolonged islet allograft survival in “high responder” recipients, in which the singular use of either modality may be ineffective.