Evidence for Raised K-Cell Levels in Type-I Diabetes

Pozzilli, Paolo; Gorsuch, A.N.; Sensi, M.; Bottazzo, Gian Franco; Cudworth, A G

doi:10.1016/s0140-6736(79)91436-3

Cited by 71 publications

(33 citation statements)

References 13 publications

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“…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].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 1983

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Summary. 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 sermn 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 ] :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 lbr 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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 1983

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“…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.…”

Section: Discussionmentioning

confidence: 99%

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

MacKay¹,

Jacobson²,

Rabinovitch³

1986

J. Clin. Invest.

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“…The metabolic compensation [15], the duration of the illness [25] and the patients' age, which is inversely correlated to the T-lymphocyte absolute number [26], are perhaps relevant. Furthermore, the IDD cases previously studied were not homogeneous from a pathogenetic point of view, immunological status differs in the various types of IDD.…”

Section: Discussionmentioning

confidence: 99%

Lymphocyte subpopulations in insulin-dependent diabetics with and without serum islet-cell autoantibodies

et al. 1981

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Summary. The lymphocyte subpopulations of 26insulin-dependent diabetics were studied. Thirteen of them had persistent pancreatic islet-cell serum antibodies (ICA) (mean (+ SD) duration of diabetes 11 + 8 years). The others were ICA-negative (mean duration of diabetes 10 + 8 years). The mean fasting blood glucose in the week before the lymphocyte count was 1.37 _ 0.45 g/l (two specimens for every patient). As controls 19 healthy volunteers, sex and age matched, were investigated. The T-lymphocyte count was no different in diabetics compared to controls~ B-cells were significantb' raised (p <0,0t) in the ICA-positive group, when tested with antihuman gammaglobulin sera (IgG + IgA + IgM), anti-human IgG and anti-human IgM, while' no difference was observed between ICA-negative patients and normal subjects. IgA-bearing lymphocytes were equally raised in both diabetic groups (p <0.05). These data show an altered immunological balance in type IB (autoimmune) diabetes, characterized by an increased number of B-lymphocytes.

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Evidence for Raised K-Cell Levels in Type-I Diabetes

Cited by 71 publications

References 13 publications

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

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

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

Lymphocyte subpopulations in insulin-dependent diabetics with and without serum islet-cell autoantibodies

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