Allogeneic hematopoietic stem cell transplantation (HSCT) can be a potential curative therapy for a variety of hematological malignancies, hematopoietic disorders, and solid tumors. However, GVHD (graft-versus-host-disease) is a major and life threating complication of allogeneic stem cell transplantation, which should be overcome. The appropriate animal model is needed for the study of GVHD and generation of anti-GVHD reagents. Recently, generation of several types of highly immunodeficient mice permits acceptance of human cells and tissues. These immunodeficient mice transplanted human peripheral blood mononuclear cell (PBMC) are currently used as the model of human-intomice xenogenic GVHD model. In this study, we established non-irradiated GVHD mice model by xeno-transplantaion of human PBMC into BALB/c Rag-2/Jak3 double deficient (BALB/c R/J) mice. Among 6 donor PBMCs (1×107 cells) transplanted into BALB/c R/J mice, 3 donor PBMCs induced typical GVHD against mice. More than 90% of the transplanted human PBMC were CD3+ T cells, and naïve T cells were differentiated into effector memory T cells and central memory T cells 4 weeks after transplantation. These results suggest that non-irradiated human-into-mice xenogenic GVHD model can be established with the selection of donors. This GVHD mice model can be a powerful tool for the study of GVHD and for the screening of anti-GVHD reagents.
