Chronic rejection of mouse kidney allografts

Roslyn B. Mannon, Jeffrey B. Kopp, Philip Ruiz, Robert Griffiths, Matilde Bustos, Jeffrey L. Platt, Paul E. Klotman, Thomas M. Coffman

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

Background. Chronic renal allograft rejection is the leading cause of late graft failure. However, its pathogenesis has not been defined. Methods. To explore the pathogenesis of chronic rejection, we studied a mouse model of kidney transplantation and examined the effects of altering the expression of donor major histocompatibility complex (MHC) antigens on the development of chronic rejection. Results. We found that long-surviving mouse kidney allografts develop pathological abnormalities that resemble chronic rejection in humans. Furthermore, the absence of MHC class I or class II antigens did not prevent the loss of graft function nor alter the pathological characteristics of chronic rejection. Expression of transforming growth factor-β (TGF-β), a pleiotropic cytokine suggested to play a role in chronic rejection, was markedly enhanced in control allografts compared with isografts. However, TGF-β up-regulation was significantly blunted in MHC- deficient grafts. Nonetheless, these differences in TGF-β expression did not affect the character of chronic rejection, including intrarenal accumulation of collagens. Conclusions. Reduced expression of either class I or II direct allorecognition pathways is insufficient to prevent the development of chronic rejection, despite a reduction in the levels of TGF-β expressed in the allograft. This suggests that the severity of chronic rejection is independent of the level of MHC disparity between donor and recipient and the level of TGF-β expression within the allograft.

Original languageEnglish (US)
Pages (from-to)1935-1944
Number of pages10
JournalKidney International
Volume55
Issue number5
DOIs
StatePublished - 1999

Keywords

  • Arteriosclerosis
  • Fibrosis
  • Glomerulosclerosis
  • Mouse MHC
  • Renal graft rejection
  • TGF-β
  • Transplantation

ASJC Scopus subject areas

  • Nephrology

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    Mannon, R. B., Kopp, J. B., Ruiz, P., Griffiths, R., Bustos, M., Platt, J. L., Klotman, P. E., & Coffman, T. M. (1999). Chronic rejection of mouse kidney allografts. Kidney International, 55(5), 1935-1944. https://doi.org/10.1046/j.1523-1755.1999.00423.x