Chronic rejection of mouse kidney allografts.

Journal Article

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-beta (TGF-beta), a pleiotropic cytokine suggested to play a role in chronic rejection, was markedly enhanced in control allografts compared with isografts. However, TGF-beta up-regulation was significantly blunted in MHC-deficient grafts. Nonetheless, these differences in TGF-beta 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-beta 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-beta expression within the allograft.

Full Text

Duke Authors

Cited Authors

  • Mannon, RB; Kopp, JB; Ruiz, P; Griffiths, R; Bustos, M; Platt, JL; Klotman, PE; Coffman, TM

Published Date

  • May 1999

Published In

Volume / Issue

  • 55 / 5

Start / End Page

  • 1935 - 1944

PubMed ID

  • 10231457

International Standard Serial Number (ISSN)

  • 0085-2538

Digital Object Identifier (DOI)

  • 10.1046/j.1523-1755.1999.00423.x

Language

  • eng

Conference Location

  • United States