Increased killer cell activity in insulin dependent (Type 1) diabetes mellitus

Abstract

Antibody dependent cell mediated cytotoxicity in relation to the levels of circulating killer cells was investigated in 16 newly diagnosed classical insulin dependent (Type 1) diabetics, 11 islet cell antibody positive non diabetic children with at least one HLA haplotype in common with their diabetic sibling, and in 15 normal controls. Antibody dependent cell mediated cytotoxicity was evaluated using, as target, 51Cr labelled human 0+ erythrocytes sensitised with an anti-CD antiserum. Killer cells were measured by the low affinity E-rosetting cell technique. Increased killer cell levels (greater than normal mean + 2SD) were accompanied by a significant enhancement in antibody dependent cell mediated cytotoxicity both in newly diagnosed diabetics (p less than 0.05) and in unaffected siblings (p less than 0.01). These preliminary results indicate that raised antibody dependent cell mediated cytotoxicity is a feature of insulin dependent diabetes at diagnosis and suggest that active B cell damage might be occurring some time before the onset of clinical symptoms.

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

“…Islet ADCC mechanisms have not been reported previously although insulin-dependent patients are described to have increased numbers of K cells and increased K cell cytotoxicity against non-islet target cells [20,21]. Others have predicted ADCC to be an important mechanism in the pathogenesis of diabetes [1].…”

Spontaneous diabetes mellitus in the Bio-Breeding/Worcester rat. Evidence in vitro for natural killer cell lysis of islet cells.

“…In contrast to the BB rat, human subjects do not demonstrate lymphopenia or defects in proportions of T and B lymphocytes (40). Abnormalities of peripheral blood lymphocyte subpopulations have been reported, however, and these include decreased T-suppressor cell numbers and activity (41)(42)(43), the presence of activated (Ia+) T cells (44,45), and increased killer cells (46) and killer cell activity (47). Killer cells are responsible for antibodydependent cell-mediated cytotoxicity.…”

Islet cell antibodies ? Theoretical and practical implications

“…The K cell acts either as an armed cell with antibodies attached, or attacks cells with an antibody bound to the surface. There is evidence that Type 1 diabetic patients have increased levels of low affinity E-rosette forming cells [22], a blood cell population shown to contain the major proportion of circulating K cells.…”