Indeed, in mouse-to-mouse models of GVHD, Treg-mediated GVHD protection is dependent on Treg activation by TNF-alpha through the TNFR2 receptor since co-transplantation of TNFR2-deficient Treg fails to attenuate GVHD (22). This evidence concerns the gene TNFRSF1B and graft versus host disease.