期刊
IMMUNOLOGY AND CELL BIOLOGY
卷 85, 期 4, 页码 338-342出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.icb.7100049
关键词
interleukin 2; regulatory T cells; Foxp3; autoimmune diseases; immune tolerance
Genetic variants of interleukin 2 (IL-2) and its receptor are associated with murine and human susceptibility to Type 1 diabetes, yet the role of IL-2 in controlling pancreatic islet-reactive T cells is unknown. Here, we develop a model where IL-2 deficiency precipitates a breakdown of self-tolerance and progression to diabetes, and its action upon diabetogenic islet- specific CD4 T cells can be tracked. We find that IL-2 is not required for Aire-dependent thymic clonal deletion of high-avidity diabetogenic clones, but is essential for thymic formation of islet- specific Foxp3-expressing CD4 T cells. The absence of IL-2 results in the expansion of low-avidity Foxp3(_) islet- reactive CD4 T cells. The mechanism by which IL-2 prevents diabetes is therefore through the establishment of a repertoire of islet- reactive Foxp3(+) T cells within the thymus, and limitation of the peripheral activation of low-avidity islet- reactive T cells that normally escape thymic negative selection.
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