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


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.

Type Journal
Authors Joo, S. Y.; Chung, Y. S.; Choi, B.; Kim, M.; Kim, J. H.; Jun, T. G.; Chang, J.; Sprent, J.; Surh, C. D.; Joh, J. W.; Kim, S. J.
Published Date 2012-12-12
Published Volume 94
Published Issue 11
Published Pages 1095-1102
Status Published in-print
DOI 10.1097/TP.0b013e318270f392
URL link to publisher's version
OpenAccess link to author's accepted manuscript version