Enhanced differentiation of functional human T cells in NSGW41 mice with tissue-specific expression of human interleukin-7.
Journal
Leukemia
ISSN: 1476-5551
Titre abrégé: Leukemia
Pays: England
ID NLM: 8704895
Informations de publication
Date de publication:
12 2021
12 2021
Historique:
pubmed:
13
5
2021
medline:
29
1
2022
entrez:
12
5
2021
Statut:
ppublish
Résumé
Humanized mouse models have become increasingly valuable tools to study human hematopoiesis and infectious diseases. However, human T-cell differentiation remains inefficient. We generated mice expressing human interleukin-7 (IL-7), a critical growth and survival factor for T cells, under the control of murine IL-7 regulatory elements. After transfer of human cord blood-derived hematopoietic stem and progenitor cells, transgenic mice on the NSGW41 background, termed NSGW41hIL7, showed elevated and prolonged human cellularity in the thymus while maintaining physiological ratios of thymocyte subsets. As a consequence, numbers of functional human T cells in the periphery were increased without evidence for pathological lymphoproliferation or aberrant expansion of effector or memory-like T cells. We conclude that the novel NSGW41hIL7 strain represents an optimized mouse model for humanization to better understand human T-cell differentiation in vivo and to generate a human immune system with a better approximation of human lymphocyte ratios.
Identifiants
pubmed: 33976371
doi: 10.1038/s41375-021-01259-5
pii: 10.1038/s41375-021-01259-5
pmc: PMC8632686
doi:
Substances chimiques
IL7 protein, human
0
Interleukin-7
0
Types de publication
Letter
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3561-3567Informations de copyright
© 2021. The Author(s).
Références
Puel A, Ziegler SF, Buckley RH, Leonard WJ. Defective IL7R expression in T(−)B(+)NK(+) severe combined immunodeficiency. Nat Genet. 1998;20:394–7.
doi: 10.1038/3877
Freeden-Jeffry von U, Vieira P, Lucian LA, McNeil T, Burdach SE, Murray R. Lymphopenia in interleukin (IL)-7 gene-deleted mice identifies IL-7 as a nonredundant cytokine. J Exp Med. 1995;181:1519–26.
doi: 10.1084/jem.181.4.1519
Peschon JJ, Morrissey PJ, Grabstein KH, Ramsdell FJ, Maraskovsky E, Gliniak BC. et al. Early lymphocyte expansion is severely impaired in interleukin 7 receptor-deficient mice. J Exp Med. 1994;180:1955–60.
doi: 10.1084/jem.180.5.1955
van Lent AU, Dontje W, Nagasawa M, Siamari R, Bakker AQ, Pouw SM. et al. IL-7 enhances thymic human T cell development in “human immune system” Rag2
doi: 10.4049/jimmunol.0902019
Rich BE, Campos-Torres J, Tepper RI, Moreadith RW, Leder P. Cutaneous lymphoproliferation and lymphomas in interleukin 7 transgenic mice. J Exp Med. 1993;177:305–16.
doi: 10.1084/jem.177.2.305
Kassar ElN, Lucas PJ, Klug DB, Zamisch M, Merchant M, Bare CV. et al. A dose effect of IL-7 on thymocyte development. Blood. 2004;104:1419–27.
doi: 10.1182/blood-2004-01-0201
Kassar ElN, Flomerfelt FA, Choudhury B, Hugar LA, Chua KS, Kapoor V. et al. High levels of IL-7 cause dysregulation of thymocyte development. Int Immunol. 2012;24:661–71.
doi: 10.1093/intimm/dxs067
Shultz LD, Lyons BL, Burzenski LM, Gott B, Chen X, Chaleff S. et al. Human lymphoid and myeloid cell development in NOD/LtSz-scid IL2R gamma null mice engrafted with mobilized human hemopoietic stem cells. J Immunol. 2005;174:6477–89.
doi: 10.4049/jimmunol.174.10.6477
Repass JF, Laurent MN, Carter C, Reizis B, Bedford MT, Cardenas K. et al. IL7-hCD25 and IL7-Cre BAC transgenic mouse lines: new tools for analysis of IL-7 expressing cells. Genesis. 2009;47:281–7.
doi: 10.1002/dvg.20497
Cosgun KN, Rahmig S, Mende N, Reinke S, Hauber I, Schäfer C. et al. Kit regulates HSC engraftment across the human-mouse species barrier. Stem Cell. 2014;15:227–38.
Mende N, Kuchen EE, Lesche M, Grinenko T, Kokkaliaris KD, Hanenberg H. et al. CCND1-CDK4-mediated cell cycle progression provides a competitive advantage for human hematopoietic stem cells in vivo. J Exp Med. 2015;212:1171–83.
doi: 10.1084/jem.20150308
Matsuda M, Ono R, Iyoda T, Endo T, Iwasaki M, Tomizawa-Murasawa M, et al. Human NK cell development in hIL-7 and hIL-15 knockin NOD/SCID/IL2rgKO mice. Life Sci Alliance. 2019;2:1–13.
doi: 10.26508/lsa.201800195
Rahmig S, Bornstein SR, Chavakis T, Jaeckel E, Waskow C. Humanized mouse models for type 1 diabetes including pancreatic islet transplantation. Horm Metab Res. 2015;47:43–7.
pubmed: 25369071
Rahmig S, Kronstein-Wiedemann R, Fohgrub J, Kronstein N, Nevmerzhitskaya A, Bornhäuser M. et al. Improved human erythropoiesis and platelet formation in humanized NSGW41 mice. Stem Cell Rep. 2016;7:591–601.
doi: 10.1016/j.stemcr.2016.08.005
Li Y, Masse-Ranson G, Garcia Z, Bruel T, Kök A, Strick-Marchand H. et al. A human immune system mouse model with robust lymph node development. Nat Methods. 2018;15:623–30.
doi: 10.1038/s41592-018-0071-6