Kobayashi Tsunehiro, Harb George, Rayat Gina R
Surgical-Medical Research Institute, Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.
Transplantation. 2005 Sep 27;80(6):821-7. doi: 10.1097/01.tp.0000173773.01811.88.
The aim of this study was to determine whether short-term administration of a combination of anti-CD154 and anti-LFA-1 monoclonal antibodies can prolong the survival of microencapsulated neonatal porcine islets (NPI) in immunocompetent mice.
Microencapsulated NPI were transplanted into the peritoneal cavity of streptozotocin-induced diabetic B6 mice that received a short-term treatment of a combination of anti-CD154 and anti-LFA-1 monoclonal antibodies. Blood glucose levels of each recipient were measured for more than 100 days posttransplantation or until graft rejection. Microcapsules were recovered to determine the presence of immune cells using immunoperoxidase staining. In addition, the levels of mouse anti-porcine immunoglobulin (Ig) G antibodies in the serum of each recipient were measured by flow cytometry.
Short-term administration of a combination of monoclonal antibodies resulted in significant prolongation of microencapsulated NPI xenograft survival. All treated mice (n = 20) achieved normoglycemia within 10-35 days posttransplantation and 11/20 mice remained normoglycemic for more than 100 days posttransplantation. In contrast, only 1/20 of the untreated mice achieved normoglycemia and this mouse became diabetic at 17 days posttransplantation. Histological examination of the recovered microcapsules from long-term surviving treated mice revealed minimal cellular overgrowth containing intact viable islets, whereas several layers of immune cells surrounding the capsules containing nonviable islets were observed in untreated mice. The levels of mouse anti-porcine IgG was also reduced in treated recipients compared to untreated mice.
These data demonstrate that short-term administration of anti-CD154 and anti-LFA-1 monoclonal antibodies can be effective in promoting long-term survival of microencapsulated NPI in immune-competent mice.
本研究的目的是确定短期给予抗CD154和抗LFA-1单克隆抗体的组合是否能延长免疫活性小鼠体内微囊化新生猪胰岛（NPI）的存活时间。
将微囊化NPI移植到经链脲佐菌素诱导的糖尿病B6小鼠的腹腔内，这些小鼠接受抗CD154和抗LFA-1单克隆抗体组合的短期治疗。在移植后100多天或直至移植物排斥时，测量每个受体的血糖水平。回收微囊，使用免疫过氧化物酶染色确定免疫细胞的存在。此外，通过流式细胞术测量每个受体血清中鼠抗猪免疫球蛋白（Ig）G抗体的水平。
短期给予单克隆抗体组合可显著延长微囊化NPI异种移植物的存活时间。所有接受治疗的小鼠（n = 20）在移植后10 - 35天内实现血糖正常，并且20只小鼠中有11只在移植后100多天仍保持血糖正常。相比之下，未治疗的小鼠中只有1/20实现血糖正常，且该小鼠在移植后17天变为糖尿病状态。对长期存活的接受治疗小鼠回收的微囊进行组织学检查发现，细胞过度生长极少，胰岛完整存活，而在未治疗的小鼠中，观察到围绕含有无活力胰岛的微囊有几层免疫细胞。与未治疗的小鼠相比，接受治疗的受体中鼠抗猪IgG水平也降低。
这些数据表明，短期给予抗CD154和抗LFA-1单克隆抗体可有效促进免疫活性小鼠体内微囊化NPI的长期存活。
