HLA incompatibility and immunogenicity of human pancreatic islet preparations cocultured with blood cells of healthy donors

Type 1 diabetes mellitus (T1D) is a T-cellmediated autoimmune disease characterized by the destruction of beta cells in the pancreas. An attractive novel therapy for type I diabetes is pancreatic islet transplantation, provided that recurrent islet autoimmunity and allograft rejection can be prevented. We analyzed the response of peripheral blood mononuclear cells (PBMC) from healthy blood donors to human islet-cell preparations with a composition similar to that of islet grafts used in clinical transplantation trials. It was examined whether the degree of major histocompatibility complex incompatibility between PBMC and donor islet cells is related to the degree of proliferative T-cell responses during coculture of human leukocyte antigen (HLA)-matched and mismatched PBMC with human islet cell-preparations (i.e., mixed islet/lymphocyte reaction). Prominent T-cell responses were observed in the vast majority of cases of double HLA class II mismatches. Intermediate T-cell responsiveness was observed in single HLA class II mismatches, whereas HLA matches did not induce a T-cell response. Our results identify the potential immunogenicity of islet preparations transplanted between HLA-DR incompatible subjects regardless of an autoimmune background of the recipient.