Anti-pancreatic immunity. In vitro studies of cellular and humoral immune reactions directed toward pancreatic islets.
It has been suggested that the immune system may be responsible for the destruction of insulin secreting cells in some types of diabetes. In order to test this hypothesis, we studied the consequences of immune-mediated reactions on the function of pancreatic islet cells in vitro. A model was set up in vitro where mouse pancreatic islet cells are exposed to human lymphocytes or sera + complement then stimulated for the release of insulin or glucagon. A selective inhibition of insulin secretion, but not of glucagon secretion, was observed in the presence of lymphocytes from 37 out of 40 insulin-dependent diabetic (IDD) patients and in the presence of sera (+ complement) from 22 out of 40. Lymphocytes were found inhibitory in almost all patients in both groups, with and without associated autoimmune diseases. In contrast, inhibitory sera were observed almost only in patients with associated autoimmune diseases or recent onset diabetes. The selective inhibition of insulin secretion, but not of glucagon secretion, suggests that lymphocytes or sera may be involved in a destructive process of insulin secreting cells in vivo. This cell-mediated effect depends on direct T lymphocyte cytotoxicity, rather than antibody-dependent cell cytotoxicity, as suggested by the lack of any effect of aggregated immunoglobulins on the reaction. In contrast, when C57BL/6 mice were immunized by mastocytoma cells from a DBA2 strain, their lymphocytes and sera blocked both secretions of insulin and glucagon when incubated in vitro with DBA2 islet cells. This non-selective inhibition may be due to anti-H2 immunity, rather than immunity directed against insulin secreting cells.
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D003165:Complement System Proteins / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005260:Female; D005934:Glucagon / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000276:immunology* / Q000378:metabolism; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008875:Middle Aged
D007136:Immunoglobulins; D007328:Insulin; D003165:Complement System Proteins; D005934:Glucagon