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 a fter in vitro exposure to 1,000 U/ml Interferon Gamma (IFN) for 48 hou rs as well as the effect of such exposure on insulin secretion and aut ologous mixed islet lymphocyte response. Flow cytometry analysis revea led that the mean fluorescence activity of both HLA-ABC (class I) and HLA-DR (class II) was significantly (p < 0.01) increased vs the contro l 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 b y flow cytometry following depletion of phagocytic cells were also qua ntified 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 gam ma exposed, DR positive insulin containing cells contained one third t he 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 insuli n secretion. Thus, pharmacologic events leading to increased fetal pan creatic interferon concentrations initiate both immune and nonimmune p rocesses that may predispose susceptible individuals to diabetes.