title: Evaluation of the efficiency of human immune system reconstitution in NSG mice and NSG mice containing a human HLA.A2 transgene using hematopoietic stem cells purified from different sources.
abstract: Severely immunodeficient mice such as the NOD/SCID/IL2rγ(null) (NSG) strain can be engrafted with human hematopoietic stem cells (HSCs), resulting in chimeric mice containing many components of the human immune system (Human Immune System mice or HIS mice). HIS mice can both support the replication of and recapitulate much of the immunological response to a variety of pathogens, including ones with strict human tropism, such as HIV-1. In an effort to develop a better mouse model for human infectious pathogen infection and possible immune resolution, we compared the human immune system reconstitution of NSG mice following injection with human CD34(+) HSCs purified from either fetal liver (FL) or umbilical cord blood (UCB). We analyzed reconstitution in standard NSG mice as well as a derivative of these mice containing an HLA.A2 encoding transgene (NSG.A2). HSCs from both sources effectively reconstituted hematopoietic lineages when injected into NSG mice. In marked contrast, total CD45(+) human hematopoietic cells in NSG.A2 mice were well reconstituted by HSCs from UCB but very poorly by HSCs purified from FL. Moreover, the reconstitution of T cell lineages in NSG.A2 mice by HSCs from UCB was inferior to that obtained using NSG mice. We also found that FL CD34(+) HSCs contain a much higher percentage of cells with a phenotype consistent with primitive progenitors than UCB HSCs. We discuss possible explanations for the influence of the HLA.A2 transgene on hematopoietic reconstitution using the two sources of HSCs.
authors.affiliation: Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA, USA; Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: John
authors.initials: J
authors.lastname: Patton
authors.affiliation: Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Raja
authors.initials: R
authors.lastname: Vuyyuru
authors.affiliation: Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Siglin
authors.affiliation: Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, PA, USA. Electronic address: Michael.Root@jefferson.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Root
authors.affiliation: Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA, USA. Electronic address: timothy.manser@jefferson.edu.
authors.forename: Tim
authors.initials: T
authors.lastname: Manser
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D002678:Chimera / Q000276:immunology; D005312:Fetal Blood / Q000166:cytology* / Q000276:immunology; D015789:HLA-A2 Antigen / Q000235:genetics* / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D006801:Humans; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008099:Liver / Q000166:cytology* / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D014183:Transplantation, Heterologous
chemical_list: D018952:Antigens, CD34; D015789:HLA-A2 Antigen; D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human
keywords: HLA-A2 transgene; Hematopoietic stem cells; Humanized mice