Lentiviral Vector Delivery of Human Interleukin-7 (hIL-7) to Human Immune System (HIS) Mice Expands T Lymphocyte Populations
Abstract
Genetically modified mice carrying engrafted human tissues provide useful models to study human cell biology in physiologically relevant contexts. However, there remain several obstacles limiting the compatibility of human cells within their mouse hosts. Among these is inadequate cross-reactvitiy between certain mouse cytokines and human cellular receptors, depriving the graft of important survival and growth signals. To circumvent this problem, we utilized a lentivirus-based delivery system to express physiologically relevant levels of human interleukin-7 (hIL-7) in Rag2-/-γc-/- mice following a single intravenous injection. hIL-7 promoted homeostatic proliferation of both adoptively transferred and endogenously generated T-cells in Rag2-/-γc-/- Human Immune System (HIS) mice. Interestingly, we found that hIL-7 increased T lymphocyte numbers in the spleens of HIV infected HIS mice without affecting viral load. Taken together, our study unveils a versatile approach to deliver human cytokines to HIS mice, to both improve engraftment and determine the impact of cytokines on human diseases.
Additional Information
© 2010 O'Connell et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Received May 30, 2010; Accepted July 14, 2010; Published August 6, 2010. Editor: Derya Unutmaz, New York University, United States of America. Funding: This study was supported by the Bill and Melinda Gates Foundation (Seattle, WA) through the Grand Challenges in Global Health Initiative (awarded to D.B.) Grand Challenge Grant #37866 (http://www.grandchallenges.org/Pages/default.aspx). R.M.O. was funded by award number K99HL102228 from the National Heart, Lung and Blood Institute (http://www.nhlbi.nih.gov/). A.B.B. is supported by amfAR fellowship #107756-47-RFVA (http://www.amfar.org). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors thank Dr. A. Berns (The Netherlands Cancer Institute, Amsterdam, The Netherlands) for providing the RAG22/2/cc2/2 mice, and thank Dr. D. Asthana at the University of Miami for performing Amplicor assays. Author Contributions: Conceived and designed the experiments: RMO ABB DB. Performed the experiments: RMO ABB CK. Analyzed the data: RMO ABB DSR LY. Wrote the paper: RMO ABB.Attached Files
Published - OConnell2010p11165PLoS_ONE.pdf
Supplemental Material - journal.pone.0012009.s001.tif
Supplemental Material - journal.pone.0012009.s002.tif
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Supplemental Material - journal.pone.0012009.s004.tif
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Additional details
- PMCID
- PMC2917362
- Eprint ID
- 19758
- Resolver ID
- CaltechAUTHORS:20100901-164229801
- Bill and Melinda Gates Foundation
- 37866
- NIH
- K99HL102228
- American Foundation for AIDS Research
- 107756-47-RFVA
- Created
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2010-09-08Created from EPrint's datestamp field
- Updated
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2021-11-08Created from EPrint's last_modified field