The interaction with PD-1 expressing CD8+ T-cells and PD-L1+ target tissues of GVHD resulted in T-cell exhaustion and apoptosis, thereby preventing acute GVHD but not chronic GVHD, which was associated with reconstitution of donor CD4+ T-cells beginning by day 21 post HSCT. Here, CD4 is linked to chronic graft versus host disease.