Yi S, Feng X, Hawthorne W, Patel A, Walters S, O'Connell P J
National Pancreas Transplant Unit, University of Sydney at Westmead Hospital, New South Wales, Australia.
Transplantation. 2000 Sep 27;70(6):896-906. doi: 10.1097/00007890-200009270-00007.
In this study, the capacity of CD8+ T cells to act as a potential effector mechanism in pancreatic xenograft rejection was examined.
The fate of pancreatic islet xenografts was studied in mice deficient in MHC class II molecules and CD4+ T cells. Fetal pig pancreas (FPP) or Wistar rat islets (RI) were transplanted into nondiabetic or streptozotocin-induced diabetic I-A knock-out (CII K/O) mice.
CII K/O mice were capable of rejecting both RI and FPP grafts. RI graft survival was not prolonged compared with wild type C57BL/6 controls. However, FPP grafts did survive longer in CII K/O recipients than in C57BL/J6 mice. Both RI and FPP graft rejection were CD8+ T-cell phenomena in CII K/O mice, as anti-CD8 monoclonal antibody prolonged graft survival, there were increased CD8+ T cells in the grafts and spleens of CII K/O recipients, and cell-mediated cytotoxicity was a CD8+ T-cell phenomenon associated with activation of the perforin/granzyme B system. By contrast, RI and FPP graft rejection was a CD4+ T cell-dependent phenomenon in wild type C57BL/6 mice with graft survival prolonged by anti-CD4 monoclonal antibody. There were increased numbers of CD4+ T cells, and cell-mediated cytotoxicity was a CD4+ T-cell phenomenon associated with activation of the Fas/FasL lytic pathway.
The results demonstrate that, in the absence of CD4+ T cells, CD8+ T cells were capable of rejecting both rat and pig pancreatic islet xenografts.
在本研究中,检测了CD8 + T细胞在胰腺异种移植排斥反应中作为潜在效应机制的能力。
在缺乏MHC II类分子和CD4 + T细胞的小鼠中研究胰岛异种移植的命运。将胎猪胰腺(FPP)或Wistar大鼠胰岛(RI)移植到非糖尿病或链脲佐菌素诱导的糖尿病I - A基因敲除(CII K/O)小鼠中。
CII K/O小鼠能够排斥RI和FPP移植物。与野生型C57BL/6对照相比,RI移植物存活时间未延长。然而,FPP移植物在CII K/O受体中的存活时间比在C57BL/J6小鼠中更长。在CII K/O小鼠中,RI和FPP移植物排斥均为CD8 + T细胞现象,因为抗CD8单克隆抗体延长了移植物存活时间,CII K/O受体的移植物和脾脏中CD8 + T细胞增加,并且细胞介导的细胞毒性是与穿孔素/颗粒酶B系统激活相关的CD8 + T细胞现象。相比之下,在野生型C57BL/6小鼠中,RI和FPP移植物排斥是CD4 + T细胞依赖性现象,抗CD4单克隆抗体可延长移植物存活时间。CD4 + T细胞数量增加,并且细胞介导的细胞毒性是与Fas/FasL裂解途径激活相关的CD4 + T细胞现象。
结果表明,在缺乏CD4 + T细胞的情况下,CD8 + T细胞能够排斥大鼠和猪的胰岛异种移植物。