CD 127- and FoxP3+ expression on CD25+CD4+ T regulatory cells upon specific diabetogeneic stimulation in high-risk relatives of type 1 diabetes mellitus patients |
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Authors: | Vrabelova Z Hrotekova Z Hladikova Z Bohmova K Stechova K Michalek J |
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Institution: | Department of Pediatrics;;Children's Neurology Department, University Hospital Motol, Prague;;Cell Immunotherapy Center, Masaryk University;;and First Department of Pediatrics, University Hospital Brno, Brno, Czech Republic |
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Abstract: | Abnormalities in CD4+CD25+ regulatory T cells (Treg) may contribute to type 1 diabetes (T1D) development. First-degree relatives of T1D patients are at increased risk especially when they carry certain HLA II haplotypes. Using two novel markers of CD4+CD25+ Treg (CD127? and FoxP3+ respectively), we evaluated number and function of Treg after specific stimulation with diabetogeneic autoantigens in 11 high-risk (according to HLA-linked risk) relatives of T1D patients and 14 age-matched healthy controls using a cytokine secretion assay based on interferon- γ (IFN- γ ) production. High-risk relatives of T1D patients had significantly lower pre- and post-stimulatory number of CD127? Treg than that of healthy controls ( P < 0.05). Labelling Treg with FoxP3+ demonstrated similar trend but did not reach statistical significance. Although the stimulation with diabetogenic autoantigens did not lead to a significant change in number of Treg in both groups, the defective function of Treg was performed by significantly higher activation of diabetogeneic T cells in high-risk relatives of T1D patients compared to healthy controls ( P ≤ 0.02). Individuals at increased HLA-associated genetic risk for T1D showed defects in Treg. |
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