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  • Type 1 diabetes  (2)
  • Fas/APO1  (1)
  • IgA/immune complexes  (1)
  • 1
    ISSN: 1432-0428
    Keywords: Type 1 diabetes ; suppressor cells ; monoclonal antibodies ; T-lymphocyte subsets ; cell-mediated immunity disorders
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Humoral and cell-mediated disorders in Type 1 (insulin-dependent) diabetes suggest that an imbalance of immunoregulatory T-cell subsets exists. In 23 newly diagnosed (onset 〈 3 months) and 21 long-standing Type 1 diabetic patients, T lymphocyte subsets were analyzed using monoclonal antibodies (OKT3, OKT4, OKT8, OKM1). The newly diagnosed patients showed a reduction with a significant difference from healthy controls in total T cells (OKT3+: 58.1 ±8.5% versus 70.7±8.0%), helper/inducer cells (OKT4+: 33.8 ±7.0% versus 47.1 ±8.3%), suppressor/cytotoxic cells (OKT8+: 18.5±7.3% versus 32 ± 6.8%) and monocytes (OKM1+: 11.5±3.8% versus 19.9±5.2%) (p〈 0.001). The long-standing diabetic patients also revealed a low number of immunoregulatory T cells compared with control subjects, although to a lesser extent (p〈 0.01–0.05). The helper/suppressor ratio (OKT4+/OKT8+) was higher in newly diagnosed patients than in control subjects (2.2±1.3 versus 1.5±0.3; p〈 0.02). When compared with 95% tolerance limits in the control subjects, the reduction of OKT8+ cells in the newly diagnosed diabetic patients appeared more marked: the mean (18.5%) coincided with the lower limit of normal subjects (18.3%). Ten of the newly diagnosed Type 1 diabetic patients had a value below the normal lower limit. Our data point to the occurrence of different immunoregulatory abnormalities in newly diagnosed Type 1 diabetic patients, especially in OKT8+ and OKT4+ cells. The imbalance in T lymphocyte subsets is further proof of the role of cellular autoimmunity in the pathogenesis of the early phases of Type 1 diabetes.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Type 1 diabetes ; Type 2 diabetes ; secretory IgA ; IgA/immune complexes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The relative contribution of secretory IgA, monomeric and polymeric IgA and IgA/secretory component-containing immune complexes was investigated in sera of diabetic patients. Secretory IgA and immune complexes containing IgA and secretory component seem to participate in the hyper-IgA of patients with Type 2 (non-insulin-dependent) diabetes only, suggesting an altered hepatic clearance via secretory component receptors on hepatocytes. In Type 1 (insulin-dependent) diabetes, the high serum IgA levels might be explained by an increase in IgA production in response to antigenic stimuli. Evidence is also accumulated that immune complexes containing IgA of mucosal origin may be involved in microangiopathy production in Type 2 diabetes.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: CD95 ; Fas/APO1 ; insulin-dependent diabetes mellitus ; cellular immunity, apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Triggering of CD95 (Fas/APO-1) cell surface receptors regulates the elimination of autoreactive T and B lymphocytes through a mechanism of cell suicide called apoptosis. Three different mutations involving CD95 or its ligand are responsible for induction of autoimmunity in susceptible mouse strains. To determine whether a defect involving the CD95 receptor is associated with human insulin-dependent diabetes mellitus (IDDM), we have studied the expression of CD95 on peripheral blood mononuclear cells from IDDM patients at different stages of the disease. Three-colour flow cytometry and mean fluorescence analysis showed that T and B lymphocytes from newly diagnosed IDDM and patients with long-standing disease, and subjects at high risk of developing the disease were highly defective in CD95 expression (p〈0.001), whereas monocytes from all the groups studied expressed normal amounts of CD95 molecules on their cell surface. T-cell subset analysis showed that the impairment of CD95 expression in IDDM patients and high-risk subjects involved both CD3+ CD4+ (p〈0.001) and CD3+ CD8+ cells (p range: 〈0.01–0.001), suggesting that this alteration concerns both helper and cytotoxic T cells. Moreover, after activation in vitro with anti-CD3 monoclonal antibody, T cells from newly diagnosed IDDM patients maintained a reduced CD95 expression during the entire cell culture period (24–72 h) in comparison to the control population (p〈0.001). In conclusion, we found a reduced expression of the apoptosis-inducing CD95 receptor on T and B lymphocytes of individuals with clinical and preclinical IDDM. We hypothesize that this defective expression may impair the capacity of autoreactive lymphocytes to undergo CD95-mediated apoptosis, contributing to the lack of control on beta-cell specific B- and T-cell clones.
    Type of Medium: Electronic Resource
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