@article{10.1172/jci.insight.96600, author = {Xiaomei Yuan AND Yi Dong AND Naoya Tsurushita AND J. Yun Tso AND Wenxian Fu}, journal = {JCI Insight}, publisher = {The American Society for Clinical Investigation}, title = {CD122 blockade restores immunological tolerance in autoimmune type 1 diabetes via multiple mechanisms}, year = {2018}, month = {1}, volume = {3}, url = {https://insight.jci.org/articles/view/96600}, abstract = {Signaling through IL-2/IL-15Rβ (CD122) is essential for the differentiation and function of T cells and NK cells. A mAb against CD122 has been implicated to suppress autoimmune type 1 diabetes (T1D) development in animal models. However, the mechanisms remain poorly understood. We find that in vivo administration of an anti-CD122 mAb (CD122 blockade) restores immune tolerance in nonobese diabetic (NOD) mice via multiple mechanisms. First, CD122 blockade selectively ablates pathogenic NK cells and memory phenotype CD8+ T cells from pancreatic islets. In contrast, islet CD4+Foxp3+ Tregs are only mildly affected. Second, CD122 blockade suppresses IFN-γ production in islet immune cells. Third, CD122 blockade inhibits the conversion of islet Th17 cells into diabetogenic Th1 cells. Furthermore, a combination of anti-CD122 mAb and Treg-trophic cytokines (IL-2 or IL-33) enhances the abundance and function of islet Tregs. In summary, these data provide crucial mechanistic insights into CD122 blockade–mediated immunoregulation and support therapeutic benefits of this combinational treatment in T1D.}, number = {2}, doi = {10.1172/jci.insight.96600}, url = {https://doi.org/10.1172/jci.insight.96600}, }