Chapter

Humanized Mice

Volume 324 of the series Current Topics in Microbiology and Immunology pp 149-165

Functional and Phenotypic Characterization of the Humanized BLT Mouse Model

  • A. K. WegeAffiliated withEmory University School of MedicineDepartment of Internal Medicine, University of Texas Southwestern Medical Center
  • , M. W. MelkusAffiliated withEmory University School of MedicineDepartment of Internal Medicine, University of Texas Southwestern Medical Center
  • , P. W. DentonAffiliated withEmory University School of MedicineDepartment of Internal Medicine, University of Texas Southwestern Medical Center
  • , J. D. EstesAffiliated withEmory University School of MedicineDepartment of Internal Medicine, University of Texas Southwestern Medical Center
  • , J. V. GarciaAffiliated withEmory University School of MedicineDepartment of Internal Medicine, University of Texas Southwestern Medical Center

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T cells play a central role in the development of immune responses. Patients lacking T cells because of genetic defects such as DiGeorge or Nezelof syndromes and patients infected with the human immunodeficiency virus are highly susceptible to infections and cancers. The lack of adequate in vivo models of T cell neogenesis have hindered the development and clinical implementation of effective therapeutic modalities aimed at treating these and other clinically important maladies. Transplantation of severe combined immunodeficient (SCID) mice with human hematopoietic stem cells results in long-term engraftment and systemic reconstitution with human progenitor, B, and myeloid cells, but curiously, human T cells are rarely present in any tissue. While the implantation of SCID mice with human fetal thymus and liver (SCID-hu thy/liv mice) allows the development of abundant thymocytes that are localized in the human organoid implant, there is minimal systemic repopulation with human T cells. However, we have recently shown that transplantation of autologous human hematopoietic fetal liver CD34 + cells into the nonobese diabetic (NOD)/SCID mouse background previously implanted with fetal thymic and liver tissues results in long-term, systemic human T cell homeostasis. In addition to human T cells, these mice have systemic repopulation with human B cells, monocytes/macrophages, and dendritic cells (DC). Importantly, in these mice the T cells developed in the human thymic implant are capable of being activated by human antigen-presenting cells and mount potent human MHC-restricted T cell immune responses.