Journal article

BIM Deficiency Protects NOD Mice From Diabetes by Diverting Thymocytes to Regulatory T Cells

Balasubramanian Krishnamurthy, Jonathan Chee, Gaurang Jhala, Prerak Trivedi, Tara Catterall, Claudia Selck, Esteban N Gurzov, Thomas C Brodnicki, Kate L Graham, Jibran A Wali, Yifan Zhan, Daniel Gray, Andreas Strasser, Janette Allison, Helen E Thomas, Thomas WH Kay



Because regulatory T-cell (Treg) development can be induced by the same agonist self-antigens that induce negative selection, perturbation of apoptosis will affect both negative selection and Treg development. But how the processes of thymocyte deletion versus Treg differentiation bifurcate and their relative importance for tolerance have not been studied in spontaneous organ-specific autoimmune disease. We addressed these questions by removing a critical mediator of thymocyte deletion, BIM, in the NOD mouse model of autoimmune diabetes. Despite substantial defects in the deletion of autoreactive thymocytes, BIM-deficient NOD (NODBim(-/-)) mice developed less insulitis and were protected fro..

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