A high incidence of insulin-dependent diabetes mellitus (IDDM) has been reported in children and young adults previously afflicted with congenital rubella syndrome (CRS). The authors have studied the effect of rubella virus infection on human pancreatic islet cells in tissue culture. These experiments were performed with the use of both monolayers and free-floating human fetal islets of Langerhans tissue. Levels of production of immunoreactive insulin by islet cells that had been infected by rubella virus were lower than those observed in control cultures, under conditions of high glucose concentration (11.1 mmol/L) in the medium. The presence of rubella viral antigens in human pancreatic beta and non-beta cells was demonstrated by double-label immunofluorescence. These results suggest that rubella virus can infect human pancreatic islet cells and that such infection may lead to significant reductions in levels of secreted insulin.

The effects of recombinant human growth hormone (GH, 1 micrograms/ml) and insulin-like growth factor I (IGF-I, 200 ng/ml) on the production of insulin and glucagon by human fetal islet-like cell clusters (ICCs) were studied in tissue culture. ICCs were derived after collagenase digestion and culture of pancreases from 16 fetuses (mean gestational age 15.6 wk). The ICCs were cultured with or without GH or IGF-I for 7 or 31 days. Basal rates of insulin and glucagon production were not altered by GH during the first 17 days of culture, but the release of both hormones was increasingly augmented by GH during the last 2 wk of culture (131% increase in insulin and 85% in glucagon compared with controls). ICCs cultured for 7 days in the presence of GH secreted more insulin when incubated for 120 min in 20 mM than in 2 mM glucose (2.1-fold response, P less than .05), whereas ICCs maintained in basal medium did not respond to glucose. GH had no effect on DNA and insulin content or insulin biosynthesis. Exogenous IGF-I caused a 28% suppression of insulin release (P less than .05) between days 4 and 10 of culture but induced a 49% increase in the mean secretion rate during the last week (days 25-31, P less than .01). Glucagon release was not affected by exogenous IGF-I. In contrast to GH, exogenous IGF-I induced a twofold increase in the DNA content of the 7-day--cultured ICCs. However, insulin biosynthesis and release were markedly suppressed.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract. Morphology, yield and function were studied in cultured islet-like cell clusters (ICC) from 140 human fetal pancreata obtained after abortions of different types performed at 11–23 weeks of gestation (12 by hysterotomy, 75 by mechanical dilation and extraction, and 53 induced with prostaglandin). After collagenase digestion and culture in medium supplemented with 10% human serum, up to 2000 free-floating ICC were formed from a single pancreas. Randomly scattered insulin- and glucagon-immunoreactive cells were found in the medullary part of the ICC. More than 100 ICC developed in 100% of the hysterotomies and 87% of the mechanical abortions, but in only 53% of the prostaglandin-induced abortions. Insulin and glucagon levels in the culture medium decreased rapidly during the first 7 days of culture, but then remained stable for at least 31 days. The hysterotomy-derived ICC responded to 10 mmol/l theophylline plus 20 mmol/l glucose by a 12.2 ± 3.1 (sem, N = 7) fold increase in insulin release, as compared with a 5.4 ± 0.9 fold response of the prostaglandin ICC (N = 16; P < 0.02). Despite the low proportion of B-cells, (pro)insulin biosynthesis accounted for 10% of the total protein biosynthesis in low (2 mmol/l) glucose. In conclusion, the yield and viability of the ICC were clearly better, if prostaglandin had not been used for the induction of the abortion.

A tissue culture system for the growth of human fetal and infantile thymic epithelial (TE) cells has been established and characterized. We have investigated the effects of infection of these cells by human cytomegalovirus (CMV), measles virus, and human immunodeficiency virus type-1 (HIV-1). In the case of CMV, morphological changes were apparent by 2-4 days after viral inoculation of infantile TE cells. CMV-related antigens were detected by immunofluorescence after 12 days, and progeny infectious CMV was recovered from culture media after 18 days. Following infection by measles virus, distinctive, multinucleated giant TE cells appeared in both cultures of fetal and infantile TE cells. Measles virus-inoculated TE cells displayed an altered phenotype, as revealed by reaction with monoclonal antibodies with specificity for a variety of TE markers. Finally, infection of TE cells by HIV-1 resulted in cellular disarrangement, increased numbers of Hassall's corpuscles, and multinucleated giant cells. An increase in the number of cells reactive with monoclonal antibodies, specific for Hassall's corpuscles, was observed in the case of cells infected by either measles virus or HIV-1. These findings suggest that a variety of different viruses can successfully infect thymic epithelial tissue. Because of the important role of the thymus in development of the immune system, it is reasonable to conclude that viral infection of thymic tissue might play an important role in virus-mediated suppression of immune responsiveness.