The in vitro immunogenicity of human pancreatic islets and acinar tissue.
thesisposted on 19.11.2015, 08:51 by Sue Swift
Islet transplantation is a relatively new treatment for Type I diabetes which offers great potential for normoglycaemia and ultimate avoidance of life- threatening complications(1). However, the treatment has only been partially successful and poor graft survival rates clinically have contrasted with reversal of diabetes by islet transplantation in rodent models. One major reason for graft loss is rejection of the islets and to study this an in vitro model for human allogeneic islet transplantation was developed. The aim of this study was to develop the mixed lymphocyte islet coculture (MLIC) and so investigate the in vitro human allogeneic lymphoproliferative response to untreated human islets. The possibility of developing a short duration MLIC as a pretransplant model for clinical use was initially investigated, and then the parameters and conditions of the MLIC response determined. Titration and kinetic studies of the MLIC (islet immunogenicity) and the MLAC (acinar tissue immunogenicity) showed that ten human islets or acinar tissue pieces (average 150mum diameter) cocultured with 1 x 10.;5 HLA mismatched responder PBLs for a duration of ninedays, gave an optimal response. Splenocyte, islet and acinar cell stimulator populations from the same donor source showed that the MLR was greater than the MLIC and the response of both were greater than the MLAC. It was shown that soluble products of untreated acinar cells inhibited lymphocyte proliferation in the MLR and may have led to a reduced MLAC response compared with that in the MLIC. Immunocytochemical investigations showed that upregulation of MHC class II antigen expression on acinar cells and induction on islets by cytokine treatment, did not enhance the stimulatory capacity in this model. The development of the MLIC as a model for in vitro islet immunogenicity showed that human islets can stimulate an allogeneic response which is not enhanced by the presence of freshly isolated acinar tissue.