Enhanced differentiation of functional human T cells in NSGW41 mice with tissue-specific expression of human interleukin-7

  • umanized 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.

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Author:Emilie CoppinORCiD, Bala Sai SundarasettyGND, Susann RahmigORCiDGND, Jonas BlumeGND, Nikita A. VerheydenORCiD, Franz BahlmannGND, Sarina RavensORCiDGND, Undine Schubert, Janine Schmid, Stefan Ludwig, Katharina GeißlerORCiDGND, Andreas KruegerORCiDGND, Orlando Guntinas-LichiusORCiDGND, Constantin von KaisenbergORCiDGND, Tanja GrotenORCiDGND, Alexander Platz, Ronald NaumannORCiD, Barbara LudwigGND, Immo PrinzORCiDGND, Claudia WaskowORCiDGND
Parent Title (German):Leukemia
Publisher:Springer Nature
Place of publication:London
Document Type:Article
Date of Publication (online):2021/05/11
Date of first Publication:2021/05/11
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2023/08/04
Page Number:7
First Page:3561
Last Page:3567
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0