title: 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.
authors: IInd Department of Pediatrics, Medical University of Białystok, Białystok, Poland. w.luczynski@wp.pl
authors: Włodzimierz
authors: W
authors: Łuczyński
authors: Natalia
authors: N
authors: Wawrusiewicz-Kurylonek
authors: Anna
authors: A
authors: Stasiak-Barmuta
authors: Remigiusz
authors: R
authors: Urban
authors: Elzbieta
authors: E
authors: Iłendo
authors: Mirosława
authors: M
authors: Urban
authors: Marek
authors: M
authors: Hryszko
authors: Adam
authors: A
authors: Kretowski
authors: Maria
authors: M
authors: Górska
mesh_terms: D000293:Adolescent; D015703:Antigens, CD / Q000235:genetics* / Q000302:isolation & purification; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics*; D015551:Autoimmunity / Q000235:genetics; D060908:CTLA-4 Antigen; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000235:genetics* / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D053450:Glucocorticoid-Induced TNFR-Related Protein / Q000235:genetics*; D006801:Humans; D060889:Inducible T-Cell Co-Stimulator Protein; D053759:Interleukin-23 / Q000235:genetics; D007378:Interleukins / Q000235:genetics; D018655:Lymphocyte Count; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051900:Smad3 Protein / Q000235:genetics; D018709:Statistics, Nonparametric; D016176:T-Lymphocyte Subsets; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D053450:Glucocorticoid-Induced TNFR-Related Protein; C556692:ICOS protein, human; D060889:Inducible T-Cell Co-Stimulator Protein; D053759:Interleukin-23; D007378:Interleukins; C464565:MYDGF protein, human; D012333:RNA, Messenger; D051900:Smad3 Protein