C. Kurts et al., Kidney protection against autoreactive CD8(+) T cells distinct from immunoprivilege and sequestration, KIDNEY INT, 60(2), 2001, pp. 664-671
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.