We demonstrated that mice receiving Lyg1-/- donor T cells alleviated aGVHD, increased long-term survival rates, showed less weight loss, lower GVHD clinical pathological scores and milder tissues damages, than mice receiving Lyg1+/+ donor T cells in CD3+ or CD4+ T cells transplanting-major MHC mismatched aGVHD model and in haplo-HSCT model. This evidence concerns the gene CD4 and graft versus host disease.