title: Systemic human T cell developmental processes in humanized mice cotransplanted with human fetal thymus/liver tissue and hematopoietic stem cells.
abstract: BACKGROUND
  In many humanized mouse models, there are few T cells in the engrafted human cell, whereas the number of B cells is high. We attempted to overcome this limitation and investigate whether the entire process of human T cell development arose similarly to the process in humans, as previously reported.
  
  
  METHODS
  To produce an advanced humanized mice model, we transplanted human fetal liver/thymus tissue subrenally and injected human CD34(+) stem cells intravenously into NOD/SCID/IL2Rgamma null (NSG) mice.
  
  
  RESULTS
  Humanized mice transplanted with fetal thymus/liver tissues and fetal liver-derived CD34(+) stem cells (FLT+FLCD34) showed higher levels of human cells and T cells than mice transplanted with fetal liver-derived CD34(+) stem cells only (FLCD34). In the transplanted thymus tissue of FLT+FLCD34 mice, thymus seeding progenitors (TSPs), early thymic progenitors (ETPs), pre-T cells, and all the other human T cell populations were identified. In the periphery, FLT+FLCD34 mice have high levels of CD45RA(+) T cells; conversely, FLCD34 mice have higher levels of CD45RO(+) T cells. The CD45RO(+) T cells of FLCD34 mice proliferated rapidly after stimulation and exhibited innate T cells properties, expressing PLZF (promyelocytic leukemia zinc finger protein).
  
  
  CONCLUSIONS
  Human T cells educated by mouse MHC II in mice without a human thymus differ from normal human T cells. On the basis of these findings, numerous T cell-tropic human diseases could be explored in our humanized mice and molecular aspects of human T cell development could be also studied extensively.
authors.affiliation: Transplantation Research Center, Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Sung-Yeon
authors.initials: SY
authors.lastname: Joo
authors.forename: Yun Shin
authors.initials: YS
authors.lastname: Chung
authors.forename: Bongkum
authors.initials: B
authors.lastname: Choi
authors.forename: Miyoung
authors.initials: M
authors.lastname: Kim
authors.forename: Jong-Hwa
authors.initials: JH
authors.lastname: Kim
authors.forename: Tae-Gook
authors.initials: TG
authors.lastname: Jun
authors.forename: Jun
authors.initials: J
authors.lastname: Chang
authors.forename: Jonathan
authors.initials: J
authors.lastname: Sprent
authors.forename: Charles D
authors.initials: CD
authors.lastname: Surh
authors.forename: Jae-won
authors.initials: JW
authors.lastname: Joh
authors.forename: Sung Joo
authors.initials: SJ
authors.lastname: Kim
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D049109:Cell Proliferation; D005434:Flow Cytometry; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D007156:Immunologic Memory; D016130:Immunophenotyping / Q000379:methods; D007371:Interferon-gamma / Q000378:metabolism; D053631:Interleukin Receptor Common gamma Subunit / Q000172:deficiency / Q000235:genetics; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008099:Liver / Q000196:embryology / Q000276:immunology; D016031:Liver Transplantation; D008213:Lymphocyte Activation; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D054504:Precursor Cells, T-Lymphoid / Q000276:immunology / Q000637:transplantation; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation*; D060168:Thymocytes / Q000276:immunology / Q000637:transplantation; D013950:Thymus Gland / Q000196:embryology / Q000276:immunology / Q000637:transplantation*; D013997:Time Factors
chemical_list: D018952:Antigens, CD34; D015415:Biomarkers; C507942:Il2rg protein, mouse; D053631:Interleukin Receptor Common gamma Subunit; D051741:Kruppel-Like Transcription Factors; D000075722:Promyelocytic Leukemia Zinc Finger Protein; C092037:ZBTB16 protein, human; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens