Donor Fas is not necessary for T-cell-mediated rejection of mouse kidney allografts

Am J Transplant. 2008 Oct;8(10):2049-55. doi: 10.1111/j.1600-6143.2008.02375.x.


It is important to resolve whether T-cell-mediated rejection (TCMR) is mediated by contact-dependent cytotoxicity or by contact-independent inflammatory mechanisms. We recently showed that the cytotoxic molecules perforin and granzymes A and B are not required for TCMR of mouse kidney transplants. Nevertheless, TCMR could still be mediated by cytotoxicity via Fas on donor cells engaging Fas ligand on host T cells. We examined whether the diagnostic TCMR lesions would be abrogated if donor Fas was absent, particularly in hosts deficient in perforin or granzymes A and B. Kidneys from Fas-deficient donors transplanted into major histocompatibility complex (MHC)- mismatched hosts developed tubulitis and diffuse interstitial infiltration indistinguishable from wild-type (WT) allografts, even in hosts deficient in perforin and granzymes A and B. Gene expression analysis revealed similar molecular disturbances in Fas-deficient and WT allografts at day 21 transplanted into WT, perforin and granzyme A/B-deficient hosts, indicating epithelial injury and dedifferentiation. Thus, donor Fas is not necessary for TCMR diagnostic lesions or molecular changes, even in the absence of perforin-granzyme mechanisms. We propose that in TCMR, interstitial effector T cells mediate parenchymal injury by inflammatory mechanisms that require neither the perforin-granzyme nor the Fas-Fas ligand cytotoxic mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Fas Ligand Protein / metabolism*
  • Gene Expression Profiling
  • Graft Rejection*
  • Granzymes / metabolism*
  • Kidney Transplantation / methods*
  • Major Histocompatibility Complex
  • Male
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Perforin / metabolism*
  • T-Lymphocytes / metabolism*
  • fas Receptor / metabolism*


  • Fas Ligand Protein
  • fas Receptor
  • Perforin
  • Granzymes