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

ABSTRACT

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 who were compared to 10 healthy children. Each child was subjected to determination of CD markers by flow cytometer. The patients group shows a significantly lower CD8[+] lymphocyte percentage [p<0.01] and significantly lower CD8[+] CD25[+] lymphocytes percentage [p<0.05] compared to control group. The CD4[+], CD4[+]/CD8[+] ratio, CD4[+] CD25[+] was not significantly different [p>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