التفاصيل البيبلوغرافية
| العنوان: |
A low antigen dose selectively promotes expansion of high-avidity autoreactive T cells with distinct phenotypic characteristics: A study of human autoreactive CD4+T cells specific for GAD65. |
| المؤلفون: |
Öling, Viveka1 (AUTHOR) viveka.oling@utu.fi, Geubtner, Kelly2 (AUTHOR), Ilonen, Jorma1,3 (AUTHOR), Reijonen, Helena2 (AUTHOR) |
| المصدر: |
Autoimmunity. Dec2010, Vol. 43 Issue 8, p573-582. 10p. 1 Chart, 3 Graphs. |
| مصطلحات موضوعية: |
*T cells, *ANTIGENS, *DIABETES, *PANCREAS, *CELL proliferation |
| مستخلص: |
T cells specific for pancreatic islet proteins can be detected in type 1 diabetes patients and at-risk individuals, suggesting a failure of the central tolerance and negative selection. We addressed the question, how antigen dose shapes the diversity of CD4+ autoreactive T cells specific for glutamate decarboxylase 65 (GAD65) in a healthy HLA-DR*0404+ individual, with a persistent GAD65-specific T-cell response. CD4+T cells from this subject were stimulated with decreasing concentrations of the GAD65 555-567 (557I) peptide, and T-cell clones were derived from the tetramer-binding cell population. Functional and structural avidity, TcR-Vβ usage, and cytokine profiles were investigated at a clonal level. T-cell clones established with a low antigen dose (0.1 and 1 μg/ml) displayed higher avidity in contrast to the clones established with the highest antigen dose (10 μg/ml; Mann-Whitney U test, p = 0.003 and 0.006, respectively). The T-cell clones stimulated with the lowest peptide dose also had a higher tetramer-binding affinity than clones stimulated with the highest dose ( p = 0.026). The majority (60.0%) of the high-avidity clones expressed TcR-Vβ5.1 chain whereas only one (12.5%) low-avidity clone did. All clones displayed Th0/Th2 cytokine profiles, but intermediate and high-avidity clones produced more IL-10 than low-avidity clones ( p = 0.032). The results demonstrate an important role of the antigen dose in the determination of characteristics of the responding T-cell repertoire. High IL-13 and IL-10 production by GAD65-reactive T cells suggests a more anti-inflammatory profile of this healthy individual underlying protection from T1D. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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