Kidney protection against autoreactive CD8(+) T cells distinct from immunoprivilege and sequestration.
BACKGROUND
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.


METHODS
RIP-mOVA transgenic mice express the model autoantigen, membrane-bound ovalbumin (mOVA), in kidney proximal tubular cells and pancreatic beta 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.


RESULTS
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.


CONCLUSIONS
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.
Kurts
C
C
Division of Nephrology and Immunology, University of Aachen, Aachen, Germany. ckurts@web.de
Klebba
I
I
Davey
G M
GM
Koch
K M
KM
Miller
J F
JF
Heath
W R
WR
Floege
J
J
D000818:Animals; D001485:Basement Membrane / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003928:Diabetic Nephropathies / Q000276:immunology; D006029:Glycosuria / Q000276:immunology; D018398:Homeodomain Proteins / Q000235:genetics; D007687:Kidney Tubules, Proximal / Q000276:immunology* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009395:Nephritis, Interstitial / Q000276:immunology* / Q000473:pathology; D010047:Ovalbumin; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D019014:fas Receptor / Q000276:immunology
D018398:Homeodomain Proteins; D011948:Receptors, Antigen, T-Cell; D019014:fas Receptor; C064658:RAG-1 protein; D010047:Ovalbumin