Contribution of Fas ligand to cardiac allograft rejection

Int Immunol. 1996 Sep;8(9):1347-54. doi: 10.1093/intimm/8.9.1347.

Abstract

Effector mechanisms for allograft injury remain unclear. In the present study, we verified the contribution of Fas and Fas ligand (FasL) to cardiac allograft rejection by utilizing the Fas-deficient lpr or FasL-deficient gld mice as the donor or recipient. Cardiac myocytes prepared from normal mice, but not those from lpr mice, constitutively expressed Fas and were susceptible to FasL-mediated lysis. Survival of cardiac allografts was substantially prolonged when gld or lpr mice were used as the recipient. In contrast, cardiac allografts from lpr mice were normally rejected without a delay. Histological examination of the grafts in the gld or lpr recipients demonstrated a lesser cellular infiltration and much milder myocyte damage. Proliferative response and cytotoxic T lymphocyte induction against the donor-type alloantigens were not impaired in the gld or lpr recipients. These results indicate a substantial contribution of FasL to cardiac allograft rejection, independent of Fas in the grafts. This ralses a possibility that FasL may be more generally involved in tissue damage associated with various diseases than expected from the expression of Fas in the target organs.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Cytotoxicity, Immunologic
  • DNA, Complementary / genetics
  • Fas Ligand Protein
  • Female
  • Fetal Heart / cytology
  • Graft Rejection / immunology*
  • Graft Rejection / pathology
  • Heart Transplantation / immunology*
  • Leukemia L5178 / pathology
  • Lymphocyte Culture Test, Mixed
  • Male
  • Membrane Glycoproteins / deficiency
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / physiology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • Mice, Mutant Strains
  • Myocardium / cytology
  • T-Lymphocytes, Cytotoxic / immunology
  • Transfection
  • Transplantation, Homologous / immunology*
  • fas Receptor / genetics
  • fas Receptor / physiology*

Substances

  • DNA, Complementary
  • Fas Ligand Protein
  • Fasl protein, mouse
  • Membrane Glycoproteins
  • fas Receptor