ABSTRACT
Immunodeficient mice are becoming invaluable tools in human stem cell and tumor research. In this study, we generated Rag-2/Jak3 double-deficient (Rag-2â»/â»Jak3â»/â») mice with a C57/BL6 and Balb/c genetic background and compared the human lymphohematopoietic cell engraftment rate. Human cord blood-derived CD34+ hematopoietic stem cells were successfully engrafted into Balb/c Rag-2â»/â»Jak3â»/â» mice; however, the engraftment rate was far lower in C57/BL6 Rag-2â»/â»Jak3â»/â» mice. Transplantation of human peripheral blood mononuclear cells resulted in the same tendency. Thus, a Balb/c background offers superior engraftment capacity than a C57/BL6 background and provides an attractive model for human hematopoietic cell engraftment.
Subject(s)
DNA-Binding Proteins/deficiency , DNA-Binding Proteins/genetics , Hematopoietic Stem Cell Transplantation , Janus Kinase 3/deficiency , Janus Kinase 3/genetics , Animals , Antigens, CD34/biosynthesis , Antigens, CD34/immunology , DNA-Binding Proteins/immunology , Flow Cytometry , Hematopoietic Stem Cells/immunology , Humans , Janus Kinase 3/immunology , K562 Cells , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, KnockoutABSTRACT
In this study, we infected NOD/Scid/Jak3null mice engrafted human peripheral blood leukocytes (hu-PBL-NOJ) with measles virus Edmonston B strain (MV-Edm) expressing hepatitis C virus (HCV) envelope proteins (rMV-E1E2) to evaluate the immunogenicity as a vaccine candidate. Although human leukocytes could be isolated from the spleen of mock-infected mice during the 2-weeks experiment, the proportion of engrafted human leukocytes in mice infected with MV (10(3)-10(5)pfu) or rMV-E1E2 (10(4)pfu) was decreased. Viral infection of the splenocytes was confirmed by the development of cytopathic effects (CPEs) in co-cultures of splenocytes and B95a cells and verified using RT-PCR. Finally, human antibodies against MV were more frequently observed than E2-specific antibodies in serum from mice infected with a low dose of virus (MV, 10(0)-10(1)pfu, and rMV-E1E2, 10(1)-10(2)pfu). These results showed the possibility of hu-PBL-NOJ mice for the evaluation of the immunogenicity of viral proteins.