Overview
Why Donor Cells Injure Host Tissues
Graft versus host disease (GVHD) occurs when immunocompetent donor T lymphocytes identify recipient tissues as foreign after an allogeneic haematopoietic stem cell transplant.
Graft-versus-host disease (GVHD) occurs when immunocompetent donor T lymphocytes identify recipient tissues as foreign after an allogeneic haematopoietic stem cell transplant. The injury develops in three linked phases: 1. Tissue injury and inflammation: Conditioning chemotherapy and radiation damage the recipient’s gut, skin, and other tissues. Damaged cells release danger signals and inflammatory cytokines that activate antigen-presenting cells. 2. Donor T-cell priming: Donor T cells recognise recipient antigens presented by these activated cells. They proliferate and differentiate into cytotoxic and inflammatory effector cells. 3. Target-organ injury: Effector T cells traffic to the skin, liver, and gastrointestinal tract in acute GVHD, where cellular injury produces rash, cholestasis, vomiting, and diarrhoea. Chronic GVHD begins with inflammation but evolves differently. Thymic injury disrupts normal T-cell selection, while abnormal T- and B-cell reconstitution promotes autoreactivity. Macrophage activation and aberrant fibroblast and collagen activity then create fibrosis. This sequence explains why chronic disease produces sclerosis, contractures, fasciitis, and small-airway fibrosis rather than only an acute inflammatory rash. The classic acute pattern involves skin, liver, and gastrointestinal tract. Chronic disease can involve the skin, mouth, eyes, liver,...