[Establishment of an xenogeneic acute graft-versus-host disease model in NOD/SCID mice by engraftment of G-CSF mobilized human mononuclear cells].

OBJECTIVE

To establish an xenogeneic acute graft-versus-host disease model by engraftment of G-CSF mobilized human mononuclear cells into NOD/SCID mice.

METHODS

Mobilized human peripheral blood mononuclear cells (PBMNCs) were transplanted into sublethally irradiated NOD/SCID mice. After transplantation, complete blood count, huCD45+ cells and other phenotype human lymphocytes were determined weekly. Mice were sacrificed, and their tissues were examined histopathologically and immunophenotypically. Genomic DNA was also prepared for detecting human beta-globin DNA sequence and endogenous mouse RAPSYN gene.

RESULTS

The human CD45+ cells in the mice appeared 1 week after transplantation. Its percentage was increased with an acute X-GVHD syndrome characterized by rapid and severe weight loss and pancytopenia. Both the specific DNAs of human beta-globin DNA gene and the murine RAPSYN gene were detected in the hu-NOD/SCID chimeras; The survival rate was 14% at 6 weeks posttransplantation. The engrafted human cells consisted mainly of CD3+ T lymphocytes but CD4/CD8 ratios seemed inverted in the chimeras. The xenogeneic graft versus host reaction was heterogeneous in different organs mainly with human lymphocytes infiltration and the liver and lungs were the critical organs.

CONCLUSION

Mobilized peripheral blood mononuclear cells are capable of engrafting in irradiated NOD/SCID mice with induced acute X-GVHD syndrome. The liver and the lungs are the critical organs. This is a good model for investigating the effects of human cells in inducing acute graft versus host disease in animal and for testing effective intervention methodology.