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

  • 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 (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, Constantin von KaisenbergORCiDGND, Alexander Platz, Ronald NaumannORCiD, Barbara LudwigGND, Immo PrinzORCiDGND, Claudia WaskowORCiDGND, Andreas KruegerORCiDGND
Parent Title (English):bioRxiv
Document Type:Preprint
Date of Publication (online):2020/05/01
Date of first Publication:2020/05/01
Publishing Institution:Universit├Ątsbibliothek Johann Christian Senckenberg
Release Date:2023/08/04
Page Number:23
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - CC BY-NC-ND - Namensnennung - Nicht kommerziell - Keine Bearbeitungen 4.0 International