| First Author | Liston A | Year | 2007 |
| Journal | Immunol Cell Biol | Volume | 85 |
| Issue | 4 | Pages | 338-42 |
| PubMed ID | 17372610 | Mgi Jnum | J:141735 |
| Mgi Id | MGI:3819327 | Doi | 10.1038/sj.icb.7100049 |
| Citation | Liston A, et al. (2007) Tracing the action of IL-2 in tolerance to islet-specific antigen. Immunol Cell Biol 85(4):338-42 |
| abstractText | 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. |
