Kidney protection against autoreactive CD8+ T cells distinct from immunoprivilege and sequestration

• Published in: Kidney international Vol. 60; no. 2; pp. 664 - 671
• Main Authors: Kurts, Christian, Klebba, Ina, Davey, Gayle M., Koch, Karl M., Miller, Jacques F.A.P., Heath, William R., Floege, Jürgen
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.08.2001; Nature Publishing; Elsevier Limited
• Subjects: Animals; Basement Membrane - immunology; Biological and medical sciences; CD8-Positive T-Lymphocytes - immunology; diabetes; Diabetic Nephropathies - immunology; fas Receptor - immunology; Fundamental and applied biological sciences. Psychology; glucosuria; Glycosuria - immunology; Homeodomain Proteins - genetics; Kidney Tubules, Proximal - immunology; Kidney Tubules, Proximal - pathology; membrane-bound ovalbumin; Mice; Mice, Knockout; Nephritis, Interstitial - immunology; Nephritis, Interstitial - pathology; Ovalbumin; proximal tubules; Receptors, Antigen, T-Cell - immunology; renoprotection; Signal Transduction - immunology; transgenic mice; tubular basement membrane; tubulointerstitial infiltration; Vertebrates: urinary system; membrane-bound ovalbumin; tubulointerstitial infiltration; transgenic mice; proximal tubules; renoprotection; tubular basement membrane; diabetes; glucosuria; Ligand; Rodentia; Transgenic animal; Kidney; Basement membrane; Antigen; Vertebrata; Renal tubule; Mammalia; Mouse; T-Lymphocyte; Infiltration; Protection
• ISSN: 0085-2538; 1523-1755
• DOI: 10.1046/j.1523-1755.2001.060002664.x

Kidney protection against autoreactive CD8+ T cells distinct from immunoprivilege and sequestration. The kidney tubulointerstitium has been reported to be protected from T-cell–mediated damage by sequestration from the T-cell compartment. We examined the ability of autoreactive T cells to infiltrate the kidney in a transgenic mouse model. RIP-mOVA transgenic mice express the model autoantigen, membrane-bound ovalbumin (mOVA), in kidney proximal tubular cells and pancreatic β cells. OVA-specific CD8+ T cells (OT-I cells) were transferred into these recipient mice and their immune response against pancreas and kidney tissue was compared. When OVA-specific CD8+ T cells (OT-I cells) were injected into RIP-mOVA mice, they were activated in the renal and pancreatic lymph nodes by cross-presentation. These in vivo-activated OT-I cells caused the destruction of pancreatic islets leading to autoimmune diabetes, but did not infiltrate the kidney. Neither CD95–CD95 ligand interactions, which have been proposed to induce apoptosis in T cells infiltrating immunologically privileged sites, nor CD30 signaling was responsible for the lack of kidney infiltration. When OT-I cells were activated in vitro prior to injection, they could infiltrate the kidney and caused acute renal failure when injected in high numbers. A mechanism distinct from previously described organ-specific protective mechanisms such as sequestration of antigen or CD95-mediated immunoprivilege contributes to the protection of the kidney tubulointerstitium from infiltration by autoreactive CD8+ T cell.