Increased in vivo frequency of IA-2 peptide-reactive IFNgamma+/IL-4- T cells in type 1 diabetic subjects |
| |
Authors: | Herzog Bernhard A Ott Patrick A Dittrich Marcus T Quast Stefan Karulin Alexey Y Kalbacher Hubert Karges Wolfram Tary-Lehmann Magdalena Lehmann Paul V Boehm Bernhard O Durinovic-Belló Ivana |
| |
Institution: | Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA. |
| |
Abstract: | Active T cell recognition of islet antigens has been postulated as the pathogenic mechanism in human type 1 diabetes, but evidence is scarce. If T cells are engaged, they are expected to display increased clonal size and exhibit a T helper (Th)1/Th2 differentiation state. We used a peptide library that covers tyrosine phosphatase IA-2, a target antigen expressed in pancreatic beta cells, to probe 8 diabetic patients and 5 HLA-matched controls. When tested in a high resolution IFNgamma/IL-4 double color ELISPOT assay directly ex vivo, the number of IA-2-reactive IFNgamma producing cells was 17-fold higher in patients than in controls and IL-4 producing cells were not present. An average of 9 peptides was recognized in the patients vs. one in the controls. Determinant recognition primarily involved CD4+ cells and showed high variability among the patients. Furthermore, anti-CD28 antibody signal enhances quantitative assessment of effector T cells in T1D patients. In vitro expansion with peptides and IL-2 results in detection of responding cells in the controls and loss of disease specificity of the T cell response. Together these data provide strong evidence for the active targeting of IA-2 by Th1 memory effector cells in human type 1 diabetes. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|