The human immune response to insulin. I. Kinetic and cellular aspects of lymphocyte proliferative responses in diabetics.
A reproducible culture system was developed with the use of peripheral blood mononuclear cells (MNC) from insulin-dependent diabetic subjects to assay T cell proliferation in response to mammalian insulins. Kinetic analysis revealed that maximal responses occur after 8 to 10 days of culture with 50 to 100 micrograms of insulin. Characterization of the cells involved showed that two cell types are required for this proliferative response: a radioresistant non-T cell and an E rosette-forming (T) lymphocyte. With the use of this assay, 16 of 32 insulin-dependent diabetics had demonstrable MNC proliferation in response to insulin or to the control antigen, tetanus toxoid. Among those 16 subjects a spectrum of responsiveness to insulin was found. Because MNC from all responsive subjects react to both beef and pork insulin, it appears that shared determinants are recognized by insulin-immune lymphocytes in this outbred population. In addition, cells from one subject were found to respond in a determinant-specific manner to the A-chain loop of beef insulin. Reproducibility of the assay was demonstrated over an 8-mo period in three experiments with the use of MNC from a single subject. This reliable assay of T lymphocyte responses to a defined antigen will help determine the fine specificity and genetic regulation of the immune response to insulin in man.
D000328:Adult; D000818:Animals; D000917:Antibody Formation; D002417:Cattle; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D000939:Epitopes; D005260:Female; D006801:Humans; D007328:Insulin / Q000276:immunology*; D007330:Insulin Antibodies / Q000276:immunology; D007700:Kinetics; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D013552:Swine; D013745:Tetanus Toxoid / Q000276:immunology
D000939:Epitopes; D007328:Insulin; D007330:Insulin Antibodies; D013745:Tetanus Toxoid