Diminished expression of ICOS, GITR and CTLA-4 at the mRNA level in T regulatory cells of children with newly diagnosed type 1 diabetes.

Abstract

Diabetes mellitus is one of the most common chronic diseases in children. T regulatory cells (Tregs) modulate response to autoantigens and probably play a role in pathogenesis of type 1 diabetes (T1DM). The aim of the present study was the assessment of T regulatory cells including their percentages and expression of critical genes in these cells in children with newly diagnosed type 1 diabetes. The examined group consisted of 50 children with T1DM. A flow cytometric analysis of T-cell subpopulations was performed using the following markers: anti-CD4, anti-CD25 and anti-CD127 (=IL-7R). Additionally, T regulatory cells were isolated for assessment of mRNA levels for chosen genes with the real-time RT-PCR technique. The percentages of CD4(+)CD25(high)CD127(dim/-) were very low and did not differ between T1DM and control children. We did not observe any statistically significant differences between healthy and diabetic children in mRNA expression for FoxP3, IL-7R (CD127), IL-8RA, IL-10RA, IL-12A, IL-2RA (CD25), IL-21, STAT1, STAT3, SOCS2, SOCS3, TGF-beta1-R1, TGF-beta-R2 and TBX-21 genes. Interestingly the mRNA level for CTLA-4, ICOS1, IL-23, IL-27, SMAD3 and GITR were lower in Treg cells of children with diabetes compared to the control patients. No disturbances in the percentages of T regulatory cells in patients with diabetes but diminished expression of some elements important in Treg function could be the result of an immunologic imbalance accompanying the onset of the diabetes. The results of our study should be used in future research in the field of immunotherapy in pediatric diabetes.

Melanoma Cells Express ICOS Ligand to Promote the Activation and Expansion of T-Regulatory Cells

“…This is in keeping with recent data showing an association of ICOS expression and IL-10-producing capacity in human Tregs and Tr1 cells (15, 26, 39). Data showing reduced ICOS + Treg frequencies in the blood and tissues of patients with autoimmune diseases such as type I diabetes further support this contention (40). …”

GITR+ regulatory T cells in the treatment of autoimmune diseases

“…In the first study, the percentages of CD4 + CD25 high CD127 dim/− cells did not differ between children with T1D and controls, but mRNA levels of CTLA-4, ICOS1, IL-23, IL-27, SMAD3, and GITR were lower in Treg cells from children with T1D [80]. In the second study of 40 T1D patients, several Treg markers, including FoxP3, were evaluated [81].…”

Low Frequency of Regulatory T Cells in the Peripheral Blood of Children with Type 1 Diabetes Diagnosed under the Age of Five

“…Minimal research has been conducted within the pediatric population. Current studies have noted a low frequency of Tregs in children with newly diagnosed T1D (Sanda et al 2008;Łuczyński et al 2009). Moreover, Sanda et al (2008) found no adverse effects of hyperglycemia and severe metabolic stress on the expression of FoxP3 and CD127.…”

“…Tregs have been implicated as a central control target in T1D progression and any defects in their development or function may represent a major predisposing factor for spontaneous autoimmunity in animals (Tritt et al 2008; Chen and Liu 2009). Some human studies have shown significantly reduced numbers of Tregs in T1D patients (Kukreja et al 2002;Łuczyński et al 2009). In contrast, other studies have not observed any differences in the frequency of these cells between diabetic patients and control subjects (Brusko et al 2005;Putnam et al 2005).…”