Immune islet killing mechanisms associated with insulin-dependent diabetes: in vitro expression of cellular and antibody-mediated islet cell cytotoxicity in humans.
Open Access
- 1 March 1983
- journal article
- research article
- Published by Oxford University Press (OUP) in The Journal of Immunology
- Vol. 130 (3) , 1189-1194
- https://doi.org/10.4049/jimmunol.130.3.1189
Abstract
Because immune mechanisms are associated with insulin-dependent diabetes, multiple organ specific and xenogeneic cytotoxicity assays were developed. Human cellular and antibody effector systems were incubated with 51Cr-labeled dispersed normal rat islet target cells. In eight of 11 diabetic patients, nonenriched mononuclear cells incubated with islet target cells were more cytotoxic than cells from age- and sex-matched controls (p less than 0.01). When non-T cell-enriched mononuclear cells were used at diabetes onset, seven of 11 patients' cells showed excessive islet cytotoxicity (p less than 0.05). In four patients showing elevated cytotoxicity at diabetes onset, cytotoxicity decreased to control levels during diabetes remission. Islet specificity was suggested in that mononuclear cells derived from diabetic subjects did not mediate cytotoxicity against rat spleen or macrophage target cells. Three cytotoxic antibody mechanisms were also evaluated. C-dependent antibody-mediated cytotoxicity with the use of patient serum-coated islet target cells was elevated above control levels in four of 14 patients. Antibody-dependent cellular cytotoxicity exceeded control values in only two of 16 patients, although four assay systems were evaluated. C-augmented antibody-dependent cellular cytotoxicity was elevated in three of 14 patients. No differences were observed for antibody-mediated mechanisms in four patients evaluated at both diabetes onset and remission. Cytotoxic antibody was present in only about one-half of the patients showing increased cellular cytotoxicity, whereas most patients expressing increased cytotoxic antibody had cellular cytotoxicity. Islet cell cytotoxicity assays with the use of effector systems from patients with recent onset insulin-dependent diabetes suggest that direct cellular cytotoxicity is more active than antibody-mediated cytotoxic mechanisms, and that cellular cytotoxicity can correlate with disease activity.This publication has 3 references indexed in Scilit:
- Cytotoxic antibodies to cloned rat islet cells in serum of patients with diabetes mellitus.Journal of Clinical Investigation, 1981
- Islet-Cell-Surface Antibodies in Juvenile Diabetes MellitusNew England Journal of Medicine, 1978
- Insulin-Dependent Diabetes: A Disease of AutoaggressionScience, 1976