Systemic human T cell developmental processes in humanized mice cotransplanted with human fetal thymus/liver tissue and hematopoietic stem cells

Sung Yeon Joo, Yun Shin Chung, Bongkum Choi, Miyoung Kim, Jong Hwa Kim, Tae Gook Jun, Jun Chang, Jonathan Sprent, Charles D. Surh, Jae Won Joh, Sung Joo Kim

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

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). CONCLUSION: 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.

Original languageEnglish
Pages (from-to)1095-1102
Number of pages8
JournalTransplantation
Volume94
Issue number11
DOIs
StatePublished - 15 Dec 2012

Keywords

  • Fetal thymus/liver
  • Human T cell development
  • Innate T cell
  • NOD/SCID/IL2Rgamma null mice

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