Prevention of CTL and NK cell-mediated cytotoxicity by microencapsulation.

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.