Title: Tracing the action of IL-2 in tolerance to islet-specific antigen
Authors: Liston, Adrian ×
Siggs, Owen M
Goodnow, Christopher C #
Issue Date: Jun-2007
Publisher: Nature publishing group
Series Title: Immunology and cell biology vol:85 issue:4 pages:338-342
Abstract: 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.
ISSN: 0818-9641
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Experimental Medicine (-)
Laboratory of Genetics of Autoimmunity
× corresponding author
# (joint) last author

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