Fas/FasL and perforin/granzyme pathway in acute rejection and diffuse alveolar damage after allogeneic lung transplantation-a human biopsy study

Virchows Arch. 2004 Oct;445(4):375-81. doi: 10.1007/s00428-004-1079-0. Epub 2004 Jul 29.


Acute rejection and diffuse alveolar damage are major problems during the early time after transplantation. Against this background, lung biopsies after allogeneic lung transplantation were studied using immunohistochemistry. Biopsies with acute rejection, diffuse alveolar damage and morphological inconspicuous biopsies were chosen. The objectives of this study were to ascertain: (a) if and how CD4 and CD8 T cells contribute to allograft rejection and diffuse alveolar damage, (b) whether there is a correlation of the chemoattractant regulated on activation normal T cells (RANTES) with the mononuclear infiltrate and (c) whether perforin/granzyme and Fas/FasL pathways contribute to lung injury after lung transplantation. Our results show that CD4(+) and CD8(+) T cells were increased in biopsies with acute rejection and, to a minor extent, also in biopsies with diffuse alveolar damage due to reperfusion injury. RANTES expression of T cells was increased in biopsies with acute rejection. Perforin seemed to have a dual role in the alloimmune response. In one regard, it had a cytolytic function in the acute rejection process, and, in contrast, it may be responsible for downregulating both CD4- and CD8-mediated alloimmune responses. The FasL/Fas pathway is not only important for induction of apoptosis during rejection but is also a mechanism of lung injury in the development of diffuse alveolar damage.

MeSH terms

  • Acute Disease
  • Adult
  • Aged
  • Biopsy
  • CD4-CD8 Ratio
  • Chemokine CCL5 / analysis
  • Fas Ligand Protein
  • Female
  • Graft Rejection / etiology
  • Graft Rejection / pathology*
  • Granzymes
  • Humans
  • Lung / pathology*
  • Lung Transplantation / immunology*
  • Male
  • Membrane Glycoproteins / physiology*
  • Middle Aged
  • Perforin
  • Pore Forming Cytotoxic Proteins
  • Serine Endopeptidases / physiology*
  • Transplantation, Homologous
  • fas Receptor / physiology*


  • Chemokine CCL5
  • FASLG protein, human
  • Fas Ligand Protein
  • Membrane Glycoproteins
  • Pore Forming Cytotoxic Proteins
  • fas Receptor
  • Perforin
  • GZMB protein, human
  • Granzymes
  • Serine Endopeptidases