Exacerbation of Spontaneous Autoimmune Nephritis Following Regulatory T Cell Depletion in B Cell Lymphoma 2-interacting Mediator Knock-out Mice

Regulatory T cells (T ) have been recognized as central mediators for maintaining peripheral tolerance and limiting autoimmune diseases. The loss of T or their function has been associated with exacerbation of autoimmune disease. However, the temporary loss of T in the chronic spontaneous disease model has not been investigated. In this study, we evaluated the role of T in a novel chronic spontaneous glomerulonephritis model of B cell lymphoma 2-interacting mediator (Bim) knock-out mice by transient depleting T . 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 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 depletion in Bim mice. This study demonstrates that transient depletion of T 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.