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J Clin Invest. 2018 Aug 1;128(8):3413-3424. doi: 10.1172/JCI97879. Epub 2018 Jul 9.

Bowman's capsule provides a protective niche for podocytes from cytotoxic CD8+ T cells.

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Division of Nephrology, Zhongshan Hospital, affiliated with Xiamen University, Xiamen, Fujian Province, China.
Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Department of Pathology, Columbia University Medical Center, New York, New York, USA.
Renal Section, James J. Peters VA Medical Center, Bronx, New York, USA.
Institute of Precision Immunology, Icahn School of Medicine at Mount Sinai, New York New York, USA.


T cells play a key role in immune-mediated glomerulonephritis, but how cytotoxic T cells interact with podocytes remains unclear. To address this, we injected EGFP-specific CD8+ T cells from just EGFP death inducing (Jedi) mice into transgenic mice with podocyte-specific expression of EGFP. In healthy mice, Jedi T cells could not access EGFP+ podocytes. Conversely, when we induced nephrotoxic serum nephritis (NTSN) and injected Jedi T cells, EGFP+ podocyte transgenic mice showed enhanced proteinuria and higher blood urea levels. Morphometric analysis showed greater loss of EGFP+ podocytes, which was associated with severe crescentic and necrotizing glomerulonephritis. Notably, only glomeruli with disrupted Bowman's capsule displayed massive CD8+ T cell infiltrates that were in direct contact with EGFP+ podocytes, causing their apoptosis. Thus, under control conditions with intact Bowman's capsule, podocytes are not accessible to CD8+ T cells. However, breaches in Bowman's capsule, as also noted in human crescentic glomerulonephritis, allow access of CD8+ T cells to the glomerular tuft and podocytes, resulting in their destruction. Through these mechanisms, a potentially reversible glomerulonephritis undergoes an augmentation process to a rapidly progressive glomerulonephritis, leading to end-stage kidney disease. Translating these mechanistic insights to human crescentic nephritis should direct future therapeutic interventions at blocking CD8+ T cells, especially in progressive stages of rapidly progressive glomerulonephritis.


Chronic kidney disease; Immunology; Nephrology; T cells

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