Soon-Shiong P, Lu Z N, Grewal I, Lanza R, Clark W
Molecular Biology Institute, University of California, Los Angeles.
Horm Metab Res Suppl. 1990;25:215-9.
Graft rejection represents one of the major barriers preventing successful pancreatic islet transplantation. Microencapsulation of isolated islets has been proposed as a potential method of overcoming this problem. We present here for the first time evidence that the biocompatible semi-permeable capsule membrane prevents cytotoxic T-lymphocyte (CTL) and natural killer (NK) cell-mediated cytotoxicity. The ability of the microcapsule to immunoisolate pancreatic and tumor cell (EL-4 and YAC-1) targets from these two mechanisms of the immune rejection response was assessed using a 51chromium-release assay. Significant cell lysis occurred when target cells were incubated with free effector cells, or with NK effector cells co-encapsulated with NK-sensitive target cells (via the release of NK cytotoxic factors (NKCF)). This effect was not observed with encapsulated effector cells alone. These results clearly demonstrate the efficacy of the microcapsule in protecting target cells against both specific cytotoxicity by CTL's, and nonspecific killing by NK cells. They also provide a method for the in vitro evaluation of the immunoprotective properties of the various new capsular materials, in terms of the effector limb or destructive phase of the allograft rejection response.
移植物排斥是阻碍成功进行胰岛移植的主要障碍之一。将分离的胰岛进行微囊化已被提议作为克服这一问题的潜在方法。我们首次在此展示证据，表明生物相容性半透性囊膜可防止细胞毒性T淋巴细胞（CTL）和自然杀伤（NK）细胞介导的细胞毒性。使用51铬释放试验评估了微囊从免疫排斥反应的这两种机制对胰腺和肿瘤细胞（EL-4和YAC-1）靶标的免疫隔离能力。当靶细胞与游离效应细胞或与与NK敏感靶细胞共包封的NK效应细胞一起孵育时（通过释放NK细胞毒性因子（NKCF）），发生了显著的细胞裂解。单独使用包封的效应细胞未观察到这种效应。这些结果清楚地证明了微囊在保护靶细胞免受CTL的特异性细胞毒性和NK细胞的非特异性杀伤方面的功效。它们还提供了一种在体外评估各种新型囊材免疫保护特性的方法，该评估涉及同种异体移植排斥反应的效应阶段或破坏阶段。
