Systemic Human T Cell Developmental Processes in Humanized Mice Cotransplanted With Human Fetal Thymus/Liver Tissue and Hematopoietic Stem Cells
- Authors
- Joo, SY[Joo, Sung-Yeon]; Chung, YS[Chung, Yun Shin]; Choi, B[Choi, Bongkum]; Kim, M[Kim, Miyoung]; Kim, JH[Kim, Jong-Hwa]; Jun, TG[Jun, Tae-Gook]; Chang, J[Chang, Jun]; Sprent, J[Sprent, Jonathan]; Surh, CD[Surh, Charles D.]; Joh, JW[Joh, Jae-won]; Kim, SJ[Kim, Sung Joo]
- Issue Date
- 15-Dec-2012
- Publisher
- LIPPINCOTT WILLIAMS & WILKINS
- Keywords
- Human T cell development; Fetal thymus/liver; NOD/
- Citation
- TRANSPLANTATION, v.94, no.11, pp.1095 - 1102
- Indexed
- SCIE
SCOPUS
- Journal Title
- TRANSPLANTATION
- Volume
- 94
- Number
- 11
- Start Page
- 1095
- End Page
- 1102
- URI
- https://scholarworks.bwise.kr/skku/handle/2021.sw.skku/63301
- DOI
- 10.1097/TP.0b013e318270f392
- ISSN
- 0041-1337
- 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 sub-renally 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.
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Collections - Medicine > Department of Medicine > 1. Journal Articles
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