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

Citation
C. Kurts et al., Kidney protection against autoreactive CD8(+) T cells distinct from immunoprivilege and sequestration, KIDNEY INT, 60(2), 2001, pp. 664-671
Citations number
31
Categorie Soggetti
Urology & Nephrology","da verificare
Journal title
KIDNEY INTERNATIONAL
ISSN journal
00852538 → ACNP
Volume
60
Issue
2
Year of publication
2001
Pages
664 - 671
Database
ISI
SICI code
0085-2538(200108)60:2<664:KPAACT>2.0.ZU;2-#
Abstract
Background. The kidney tubulointerstitium has been re ported to be protecte d from T-cell-mediated damage by sequestration from the T-cell compartment. We examined the ability of autoreactive T cells to infiltrate the kidney i n a transgenic mouse model. Methods. RIP-mOVA transgenic mice express the model autoantigen. membrane-b ound ovalbumin (mOVA). in kidney proximal tubular cells and pancreatic beta cells. OVA-specific CD8+ Tcells (OT-I cells) were transferred into these r ecipient 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 destructi on of pancreatic islets leading to autoimmune diabetes, but did not infiltr ate the kidney. Neither CD95-CD95 ligand interactions, which have been prop osed to induce apoptosis in T cells infiltrating immunologically privileged sites, nor CD30 signaling was responsible for the lack of kidney infiltrat ion. 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 imm unoprivilege contributes to the protection of the kidney tubulointerstitium from infiltration by autoreactive CD8+ T cell.