The Pathophysiology of Graft-versus-Host Disease

Acute graft-versus-host disease (GVHD) results from complex interactions between donor T cells and host tissues in an inflammatory mulieu. The pathophysiology of acute GVHD can be considered as a three-step process involving both the innate and adaptive immune systems. The three steps are tissue damage in the recipient by the conditioning regimen, donor T-cell activation and clonal expansion, and cellular and inflammatory factors. Complications of HCT, particularly GVHD, remain major barriers to the wider application of allogeneic HCT for a variety of diseases. Recent advances in the understanding of cytokine networks, and also the direct mediators of cellular cytotoxicity, have led to improved understanding of this complex disease process. Tissue injury related to the conditioning regimen or infection is amplified by direct cytotoxicity via perforin/granzyme and Fas/FasL pathways, through direct cytokine-induced damage, and by recruitment of secondary effectors such as granulocytes and monocytes.