Systemic human T cell developmental processes in humanized mice cotransplanted with human fetal thymus/liver tissue and hematopoietic stem cells
SCIE
SCOPUS
- Title
- Systemic human T cell developmental processes in humanized mice cotransplanted with human fetal thymus/liver tissue and hematopoietic stem cells
- Authors
- Joo, SY; Chung, YS; Choi, B; Kim, M; Kim, JH; Jun, TG; Chang, J; Sprent, J; Surh, CD; Joh, JW; Kim, SJ
- Date Issued
- 2012-12-15
- Publisher
- Lippincott Williams & Wilkins
- 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.
- Keywords
- Human T cell development; Fetal thymus/liver; NOD/SCID/IL2Rgamma null mice; Innate T cell; THYMOCYTE-THYMOCYTE INTERACTION; IMMUNE-RESPONSES; DIFFERENTIATION; MODEL; TRANSPLANTATION; EXPRESSION; EFFECTOR; MOUSE; BLOOD
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/15175
- DOI
- 10.1097/TP.0B013E318270F392
- ISSN
- 0041-1337
- Article Type
- Article
- Citation
- Transplantation, vol. 94, no. 11, page. 1059 - 1102, 2012-12-15
- Files in This Item:
- There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.