Human Beta-Cell Lines as Tools to Study Immune Protection Strategies in Diabetes

Genetically engineered human beta-cell lines provide a novel tool to study the pathogenesis of type 1 diabetes and to develop alternative beta-cell replacement therapy[1]. The immune system is essentially involved in type 1 diabetes and beta-cell transplantation. We assessed the interaction of human beta cell lines with the immune system to resolve their potential for immune intervention protocol studies. Human pancreatic beta-cell lines derived from vir ally tranduced fetal beta-cells were co-cultured with alloreactive cytotoxic T-cells, proinflammatory cytokines from activated autoreactive Th1 cells or NK-cells in presence or absence of alloreactive antibodies. Beta-cell lines were pre-conditioned with Th1 cytokines or supernatant or high glucose to mimic inflammatory and hyperglycemia-stressed conditions. Beta-cell viability was assessed by chromium release and propidium iodides staining. Low HLA expression protected human beta-cell lines from adaptive immune destruction, but was associated with direct killing by activated NK-cells. Autoreactive Th1 cell inflammation, rather than glucose stress, induced increased beta-cell apoptosis and up regulation of HLA, increasing their vulnerability to killing by alloreactive cytotoxic T-cells and alloreactive antibody mediated killing through NK-cells. Genetically engineered human beta-cell lines are useful targets to study diverse immune responses that may be involved in the pathogenesis of T1D in humans. The use of beta-cells in immune assays may assist to evaluate novel immune intervention tools to interfere in type 1 diabetes pathogenesis and beta-cell protection protocols for transplantation.