Mouse models of graft-versus-host disease

Allogeneic hematopoietic cell transplantation (HCT) represents an important therapy for many hematological and some epithelial malignancies and for a spectrum of nonmalignant diseases (Appelbaum, 2001). The development of novel strategies such as donor leukocyte infusions (DLI), nonmyeloablative HCT and cord blood transplantation (CBT) have helped expand the indications for allogeneic HCT over the last several years, especially among older patients (Welniak et al., 2007). However, the major toxicity of allogeneic HCT, Graft-Versus-Host disease (GVHD), remains a lethal complication that limits its wider application (Ferrara and Reddy, 2006). Depending on when it occurs after HCT, GVHD can be either acute or chronic (Deeg, ; Weiden et al., ; Weiden et al., ; Lee, 2005). Acute GVHD is responsible for 15% to 40% of mortality and is the major cause of morbidity after allogeneic HCT, while chronic GVHD occurs in up to 50% of patients who survive three months after HCT. Mouse models have provided the majority of insights into the biology of this complex disease process.