An early study by Blazar et al. (46) showed that blockade of CTLA-4 at an early time point during allo-HCT augmented alloreactivity, resulting in accelerated GVHD lethality in a major histocompatibility complex (MHC) mismatched mouse model of bone marrow transplantation (BMT). The gene discussed is CTLA4; the disease is graft versus host disease.