Immune islet killing mechanisms associated with insulin-dependent diabetes: Three rabbit antibody-mediated islet cell cytotoxicity models

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Abstract
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 antibodymediated cytotoxicity, 1∶10 for antibody-dependent cellular cytotoxicity and 1∶1000 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.