Zhang Y Clare, Pileggi Antonello, Molano R Damaris, Wasserfall Clive, Campbell-Thompson Martha, Ricordi Camillo, Atkinson Mark A, Inverardi Luca
Department of Pediatrics, Children's Research Institute, University of South Florida, St. Petersburg, FL, USA.
Transplantation. 2005 Aug 27;80(4):530-3. doi: 10.1097/01.tp.0000168212.53172.06.
Interleukin (IL)-10 has proven effective in various allogeneic transplantation models and for preventing recurrent autoimmune rejection of syngeneic islets in NOD mice. Therefore, we evaluated systemic IL-10 overexpression on allogeneic islet graft survival. Diabetic NOD mice received a single injection of recombinant adeno-associated virus (rAAV) serotype 2 encoding murine IL-10 (rAAV-IL-10) four weeks prior to renal subcasular islet transplantation. In a model having both autoimmune and allogeneic responses, IL-10 failed to protect C57BL/6 islets in spontaneously diabetic NOD mice. In an allograft model (C57BL/6 islets into young male streptozotocin-induced diabetic NOD mice), long-term (i.e., >169 days) islet survival was only seen in 2 of 14 rAAV-IL-10 treated mice. These failures occurred despite in vivo IL-10 production at transplant previously associated with protection of syngeneic islet grafts in NOD mice. Thus, IL-10 appears insufficient in protecting transplanted islet cells from allogeneic rejection and suggests important mechanistic variances between alloreactivity and autoimmunity in terms islet graft loss.
白细胞介素（IL）-10已被证明在各种同种异体移植模型中有效，并且可用于预防非肥胖糖尿病（NOD）小鼠同基因胰岛的复发性自身免疫排斥反应。因此，我们评估了全身IL-10过表达对同种异体胰岛移植存活的影响。糖尿病NOD小鼠在肾包膜下胰岛移植前四周接受单次注射编码小鼠IL-10的重组腺相关病毒（rAAV）2型（rAAV-IL-10）。在一个同时具有自身免疫和同种异体反应的模型中，IL-10未能保护自发糖尿病NOD小鼠中的C57BL/6胰岛。在同种异体移植模型（将C57BL/6胰岛移植到年轻雄性链脲佐菌素诱导的糖尿病NOD小鼠中）中，在14只接受rAAV-IL-10治疗的小鼠中，只有2只观察到长期（即>169天）胰岛存活。尽管移植时体内产生IL-10，而这在之前与保护NOD小鼠同基因胰岛移植相关，但仍出现了这些失败情况。因此，IL-10似乎不足以保护移植的胰岛细胞免受同种异体排斥，这表明在胰岛移植丢失方面，同种异体反应性和自身免疫性之间存在重要的机制差异。
