A 2-hit model for chronic GVHD.

In this issue of Blood, Dertschnig and colleagues1 demonstrate in mice that acute graft-versus-host disease (GHVD) results in a marked reduction of autoimmune receptor–expressing medullary thymic epithelial cells (Aire1 mTEC) and a decrease in the diversity of Aire-dependent tissue-restricted peripheral selfantigens (TRAs) required for effective negative thymic selection. Both of these abnormalities are reversed by the peritransplant administration of the epithelial protectant drug, fibroblast growth factor 7(Fgf7).