HUMAN FETAL ISLET RESPONSE TO INTERFERON-GAMMA

Investigation was made of the ability of human fetal islets to express major histocompatibility complex class I and class II gene products after in vitro exposure to 1,000 U/ml Interferon Gamma (IFN) for 48 hours as well as the effect of such exposure on insulin secretion and autologous mixed islet lymphocyte response. Flow cytometry analysis revealed that the mean fluorescence activity of both HLA-ABC (class I) and HLA-DR (class II) was significantly (p < 0.01) increased vs the control after IFN incubation. (class I: Control = 125 +/- 35 SD, IFN = 995 +/- 418 S.D.; class II: Control = 70 +/- 30 SD, IFN = 300 +/- 74 S.D.). Cells containing surface expression of DR and intracellular insulin by flow cytometry following depletion of phagocytic cells were also quantified and increased from 0 to 0.67 percent following exposure to IFN. Autologous splenocytes responded to cells previously incubated with IFN with a three fold increase in H-3-thymidine uptake. Interferon gamma exposed, DR positive insulin containing cells contained one third the insulin of DR negative insulin containing cells (2.1 +/- 1.5 vs 6.6 +/- 3.4 mu U/cell) but were nevertheless capable of stimulated insulin secretion. Thus, pharmacologic events leading to increased fetal pancreatic interferon concentrations initiate both immune and nonimmune processes that may predispose susceptible individuals to diabetes.