Tissue injury and repair in allografts: novel perspectives

Curr Opin Nephrol Hypertens. 2003 May;12(3):259-66. doi: 10.1097/00041552-200305000-00006.


Purpose of review: Recent research achievements might considerably alter scientific concepts of pathways involved in tissue injury and repair.

Recent findings: Accumulating evidence for an important role of alloantibodies in acute and chronic allograft rejection led to a renewed interest in humoral kidney transplant rejection. Studies reassessing the mechanisms of antibody- and complement-mediated injury now shed new light on the pathogenic mechanisms underlying acute or chronic graft dysfunction and injury. A closer look at humoral effector mechanisms revealed that endothelial cell activation and injury may play a key role in humoral rejection, and further uncovered an important interplay between humoral and cellular alloimmunity. Regeneration of cells after injury has been thought to rely on activation of local progenitor cells. Recent investigation indicates that regeneration of grafted solid organs is not exclusively based on self-renewal of tissues but obviously also involves repopulation of the graft by recipient cells, creating chimerism in the vasculature and other compartments. Besides reparative compensation of cell loss, chimerism of endothelial cells might also alter immunologic properties of the graft, thus favoring adaptation and graft survival. On the other hand, however, myofibroblasts mediating deleterious arterial intimal proliferation may also be of recipient origin. A possible source of graft-repopulating recipient cells are bone marrow-derived adult stem cells with the amazing capacity of differentiating into cell types of all three germ cell layers.

Summary: Reliable diagnosis of humoral mechanisms in allograft rejection and identification of involved effector mechanisms should provide the basis for development and targeted application of specific anti-humoral treatment. Recently emerged new concepts of mechanisms underlying tissue regeneration might pave the way for entirely new therapeutic approaches in human disease.

Publication types

  • Review

MeSH terms

  • Adaptation, Physiological
  • Animals
  • Complement C4 / metabolism
  • Complement C4b*
  • Complement System Proteins / metabolism
  • Female
  • Graft Rejection / immunology
  • Graft Rejection / pathology
  • Graft Rejection / physiopathology
  • Humans
  • Isoantibodies / biosynthesis
  • Kidney Transplantation / immunology
  • Kidney Transplantation / pathology*
  • Kidney Transplantation / physiology
  • Male
  • Peptide Fragments / metabolism
  • Regeneration
  • Stem Cells / pathology
  • Transplantation, Homologous


  • Complement C4
  • Isoantibodies
  • Peptide Fragments
  • Complement C4b
  • complement C4d
  • Complement System Proteins