Exacerbation of spontaneous autoimmune nephritis following regulatory T cell depletion in B cell lymphoma 2‐interacting mediator knock‐out mice

Summary Regulatory T cells (T regs ) have been recognized as central mediators for maintaining peripheral tolerance and limiting autoimmune diseases. The loss of T regs or their function has been associated with exacerbation of autoimmune disease. However, the temporary loss of T regs in the chronic spontaneous disease model has not been investigated. In this study, we evaluated the role of T regs in a novel chronic spontaneous glomerulonephritis model of B cell lymphoma 2‐interacting mediator (Bim) knock‐out mice by transient depleting T regs . Bim is a pro‐apoptotic member of the B cell lymphoma 2 (Bcl‐2) family. Bim knock‐out (Bim –/– ) mice fail to delete autoreactive T cells in thymus, leading to chronic spontaneous autoimmune kidney disease. We found that T reg depletion in Bim –/– mice exacerbated the kidney injury with increased proteinuria, impaired kidney function, weight loss and greater histological injury compared with wild‐type mice. There was a significant increase in interstitial infiltrate of inflammatory cells, antibody deposition and tubular damage. Furthermore, the serum levels of cytokines interleukin (IL)−2, IL‐4, IL‐6, IL‐10, IL‐17α, interferon (IFN)‐γ and tumour necrosis factor (TNF)‐α were increased significantly after T reg depletion in Bim –/– mice. This study demonstrates that transient depletion of T regs leads to enhanced self‐reactive T effector cell function followed by exacerbation of kidney disease in the chronic spontaneous kidney disease model of Bim‐deficient mice.