The Pathophysiology of Acute Graft-versus-Host Disease

James L.M. Ferrara, Kenneth R. Cooke, Takanori Teshima

Research output: Contribution to journalReview articlepeer-review

164 Scopus citations


The pathophysiology of acute graft-versus-host disease (GVHD) is a complex process that can be conceptualized in three phases. In the first phase, high-dose chemoradiotherapy causes damage to host tissues, including a self-limited burst of inflammatory cytokines such as tumor necrosis factor (TNF)-α and interleukin 1. These cytokines activate host antigen-presenting cells (APCs). In the second phase, donor T-cells recognize alloantigens on host APCs. These activated T-cells then proliferate, differentiate into effector cells, and secrete cytokines, particularly interferon (IFN)-γ. In the third phase, target cells undergo apoptosis mediated by cellular effectors (eg, donor cytotoxic T-lymphocytes) and inflammatory cytokines such as TNF-α. TNF-α secretion is amplified by stimuli such as endotoxin that leaks across damaged gastrointestinal mucosa injured by the chemoradiotherapy in the first phase. TNF-α and IFN-γ cause further injury to gastrointestinal epithelium, causing more endotoxin leakage and establishing a positive inflammatory feedback loop. These events are examined in detail in the following review.

Original languageEnglish
Pages (from-to)181-187
Number of pages7
JournalInternational Journal of Hematology
Issue number3
StatePublished - Oct 2003
Externally publishedYes


  • Bone marrow transplantation
  • Cytokines
  • Graft-versus-host disease
  • IL-1β
  • TNF-α


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