Highly Sensitive Model for Xenogenic GVHD Using Severe Immunodeficient NOG Mice

BACKGROUND: Several animal models for xenogenic (xeno) graft versus host disease (GVHD) have been developed in immunodeficient mice, such as C.B-17-scid and nonobese diabetes (NOD)/severe combined immunodeficiency (SCID), by human peripheral blood mononuclear cell (hPBMC) transplantation. However, these models pose problems because they require sublethal total body irradiation of the mice and a large number of hPBMCs to induce GVHD, and the timing of onset of GVHD is also unstable. The aim of this study is to establish improved murine models of xeno-GVHD using novel immunodeficient NOD/Shi-scid IL2r gamma null (NOG) mice. METHODS: In three strains of immunodeficient mice, NOG, BALB/cA-RAG2 IL2r gamma null, and NOD/SCID mice, GVHD was induced by transplantation of hPBMCs with or without total body irradiation, and the GVHD symptoms in these strains were compared. RESULTS: After intravenous transplantation of hPBMCs, NOG mice showed early onset of GVHD symptoms and a small number of hPBMCs (2.5 x 10(6)) was sufficient to induce GVHD when compared with BALB/cA-RAG2 null IL2r gamma null and NOD/SCID mice. In addition, total body irradiation was not always necessary in the present model. CONCLUSIONS: These results indicate that our model using the NOG mouse is a useful tool to investigate GVHD and to develop effective drugs for GVHD.