Lymphocyte apoptosis in the pathogenesis of type 1 diabetes mellitus

Beta cell apoptosis has been associated with insulin dependent diabetes mellitus [IDDM] onset in newly diagnosed diabetic patients. There is an emerging evidence that T cell-induced apoptosis is a dominant effector mechanism in diabetes mellitus type 1 [DM1]. Pancreatic/3-cells derived from newly diagnosed type 1 diabetics were found to have increased cell surface expression of Fas [CD95] compared to/3-cells from healthy subjects. The study investigates the spontaneous lymphocyte apoptosis via CD95 molecule expression to demonstrate activation induced cell death in children with high risk of DM1 and in type 1 diabetics under insulin therapy. This study comprised 90 children and adolescents, divided into 3 groups. GO] comprised 40 type-1 diabetics, their ages ranging from 8.0 to 17.0 years and disease duration between 2.0 and 12.0 years. G[2] [prediabetics] included 30 euglycaemic subjects who were first degree, relatives of type 1 diabetics, with normal fasting blood glucose and positive, first phase insulin release [FPIR] and/or positive islet cell [ICA] or glutamic acid decarboxylase [GAD] antibodies. G[3] comprised 20 healthy, age and sex matched subjects with no clinical or laboratory signs or family history of type-1DM Patients were subjected to clinical evaluation with special emphasis on signs suggestive of microvascular complications. The study measurements included random blood sugar [RBS], glycosylated hemoglobin [HbA1], urinary microalbumin assay and flow cytometric assessment of apoptosis by measuring CD95 percentage expression on CD3 lymphocytes. The percentage of CD95 positive T-lymphocytes was significantly higher in prediabetics than in type-1diabetics and controls [57.687 +/- 6.68, 45.01 +/- 6. 648,16.75 +/- 4.98% respectively; p<0. 001]. CD3 positive bnphocytes were significantly lower in prediabetics than type-1 diabetics controls [52.93 +/- 11.64, 66.23 +/- 7.04, 63.910 +/- 3.4% respectively, p<0.001]. The percentage of CD95 on T-lymphocytes could not be Correspondence: correlated with age, insulin dose and RBS, but HbA1 was positively correlated with both CD3 lymphocytes and CD95% expression. Complicated type-1 diabetics showed higher CD95% expression compared to non-complicated patients. Peripheral blood lymphocytes with CD95 antigen expression re increased in prediabetics. As CD95 is an important receptor for activation-induced cell death, CD95 mediated apoptosis could play a j potential role in the pathogenesis of DM1

Cell-mediated immunity in recent-onset type 1 diabetic children

The ability to suppress an immune response makes regulatory T-cells [T-reg] an attractive candidate as a novel therapeutic agent for treating autoimmune diseases. The mechanisms involved in maintenance of peripheral tolerance include a specialized subset of regulatory-T-cells [T-reg] within the T-cell population. The CD4[+] CD25[+] T-cells may be, important in modulating the risk for autoimmunity. Auto-reactive cytotoxic-cells recognize peptide epitopes displayed on the beta cells surface in the context of HLA class] molecules. A population of CD8[+] regulatory T-cells characterized by expression of CD25 and FOXP3 have been identified and induced in the human peripheral blood cells. The regulatory activity of these cells is on autologous, antigen-reactive CD4[+] T-cells in a cell contact-dependent manner. These findings provide an evidence for a new mechanism for induction of immune regulation in human. This study was aiming to assess the cellular immune parameters including the percentage of CD4[+], CD8[+], CD4[+]/CD8[+] ratio,CD4[+]CD25[+], CD8[+] CD25[+] lymphocytes, which may have its application in developing immune therapy based tools for halting disease progression. This study was conducted on 20 children of recent onset type 1 diabetes [disease duration 0.05] between the two groups. A significant inverse correlation was found between CD4[+] CD25[+] T-cells and HbA1c percentage among patients group [p<0.05].Also a significant difference in the percentage of CD4[+] CD25[+] T-cells was found when patients with HbA1c<8%w ere compared to those with HbA1c >/= 8% [the latter group had significantly lower percentage of CD4[+] CD8[+] T-cells]. Type 1 diabetes is characterised at its onset by a lowered percentage of CD8[+] and CD8[+] CD25[+] T-cells in peripheral blood, a normal percentage of CD4[+] and CD4[+] CD25[+] T-cells. There may be an inverse correlation between percentage of CD4[+] CD25[+] T-cells at disease onset and HbA1c level after three months. These data support the hypothesis that a defect in function or deficiency in number of T-regulatory cells may affect the pathogenesis of type 1 diabetes