Immune islet killing mechanisms associated with insulin-dependent diabetes: three rabbit antibody-mediated islet cell cytotoxicity models.
Antibody-mediated islet cell killing mechanisms have been associated with human insulin-dependent diabetes. Several types of antibody-mediated cytotoxic mechanisms exist, but only complement-dependent antibody-mediated cytotoxicity is reported for islet killing. To evaluate further islet cytotoxic antibody mechanisms, we have studied antibody-dependent cellular cytotoxicity and complement augmented antibody-dependent cellular cytotoxicity using polyclonal rabbit anti-rat islet cell immune serum and 51Cr-labelled dispersed normal rat islet target cells. Maximal immune serum-mediated islet cell specific cytotoxicity was 80% for complement-dependent antibody-mediated cytotoxicity, 40% for antibody-dependent cellular cytotoxicity and 20% for complement-augmented antibody-dependent cellular cytotoxicity. The minimum serum dilution for maximal islet cell cytotoxicity was 1:100 for complement-dependent antibody-mediated cytotoxicity, 1:10 for complement-augmented antibody-dependent cellular cytotoxicity. These data indicate a unique optimal serum dilution for each of the three antibody killing mechanisms. Immune serum-mediated cytotoxicity was more specific for rat islet target cells than macrophage target cells. That antibody mediated these cytotoxic events was documented using immune serum-derived, DEAE purified immunoglobulin G which induced killing in all three antibody assays. Both antibody-dependent cellular cytotoxicity assays appear useful for studies of human diabetes, since human non-T mononuclear cells are cytotoxic to islet cells. These results suggest that for studies of potential islet cell killing mechanisms in insulin-dependent diabetes, specific xenogeneic assays exist not only for complement-dependent antibody-mediated islet cytotoxicity, but also for antibody-dependent cellular cytotoxicity and complement augmented antibody-dependent cellular cytotoxicity.
D000293:Adolescent; D000328:Adult; D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity; D003165:Complement System Proteins / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005260:Female; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D007515:Islets of Langerhans / Q000276:immunology*; D008297:Male; D011817:Rabbits; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains
D007106:Immune Sera; D003165:Complement System Proteins