James R F, Lake S P, Chamberlain J, Thirdborough S, Bassett P D, Mistry N, Bell P R
Department of Surgery, Leicester Royal Infirmary, United Kingdom.
Transplantation. 1989 Jun;47(6):929-33. doi: 10.1097/00007890-198906000-00001.
In this study we have examined the use of low-dose gamma-irradiation for the reduction of islet immunogenicity in the strong allogeneic combination of WAG rat islets transplanted into diabetic AUG recipients. First, we determined that gamma-irradiation reduced immunogenicity in vitro by use of a modified MLR with WAG islets as stimulators and AUG splenocytes as responders. We then determined the maximum dose of gamma-irradiation that could be used (250 rads) before islet function was affected. As 250 rads islet pretreatment alone was ineffective in prolonging allograft survival, we combined the pretreatment with a short course (days 0, 1, 2; 30 mg/kg) of cyclosporine. We found that CsA was only effective in significantly prolonging allograft survival when given subcutaneously in olive oil. The CsA treatment alone gave a significantly prolonged survival time for the islet allografts (median, 37 days vs. 6 days for controls), but when combined with the 250 rads islet pretreatment a synergistic effect was seen with 100% becoming long-term survivors (greater than 100 days). The long-term surviving AUG rats from both the CsA alone group and the CsA plus 250 rads pretreated islets group were challenged with WAG dendritic cells (DC). The islets from the 250 rads pretreated group were subsequently rejected (day 6) while the CsA alone group were not affected. The role of low dose gamma-irradiation when combined with CsA treatment of islet graft recipients in inducing specific unresponsiveness will be discussed.
在本研究中，我们检测了低剂量γ射线照射对降低WAG大鼠胰岛移植到糖尿病AUG受体中的强同种异体组合的胰岛免疫原性的作用。首先，我们通过使用改良的混合淋巴细胞反应（MLR），以WAG胰岛作为刺激细胞，AUG脾细胞作为反应细胞，确定γ射线照射在体外降低了免疫原性。然后，我们确定了在胰岛功能受到影响之前可以使用的γ射线照射的最大剂量（250拉德）。由于单独的250拉德胰岛预处理在延长同种异体移植存活期方面无效，我们将该预处理与短疗程（第0、1、2天；30mg/kg）的环孢素联合使用。我们发现，环孢素只有在以橄榄油皮下给药时才有效地显著延长同种异体移植的存活期。单独的环孢素治疗使胰岛同种异体移植的存活时间显著延长（中位数，37天对对照组的6天），但当与250拉德胰岛预处理联合使用时，观察到协同效应，100%的动物成为长期存活者（大于100天）。来自单独环孢素组和环孢素加250拉德预处理胰岛组的长期存活的AUG大鼠用WAG树突状细胞（DC）进行攻击。来自250拉德预处理组的胰岛随后被排斥（第6天），而单独环孢素组未受影响。将讨论低剂量γ射线照射与环孢素治疗胰岛移植受体联合使用时在诱导特异性无反应性方面的作用。
