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Coppin E, Sundarasetty BS, Rahmig S, et al. Enhanced differentiation of functional human T cells in NSGW41 mice with tissue-specific expression of human interleukin-7. Leukemia. 2021;35(12):3561-3567doi: 10.1038/s41375-021-01259-5.
Coppin, E., Sundarasetty, B. S., Rahmig, S., Blume, J., Verheyden, N. A., Bahlmann, F., Ravens, S., Schubert, U., Schmid, J., Ludwig, S., Geissler, K., Guntinas-Lichius, O., von Kaisenberg, C., Groten, T., Platz, A., Naumann, R., Ludwig, B., Prinz, I., Waskow, C., & Krueger, A. (2021). Enhanced differentiation of functional human T cells in NSGW41 mice with tissue-specific expression of human interleukin-7. Leukemia, 35(12), 3561-3567. https://doi.org/10.1038/s41375-021-01259-5
Coppin, Emilie, et al. "Enhanced differentiation of functional human T cells in NSGW41 mice with tissue-specific expression of human interleukin-7." Leukemia vol. 35,12 (2021): 3561-3567. doi: https://doi.org/10.1038/s41375-021-01259-5
Coppin E, Sundarasetty BS, Rahmig S, Blume J, Verheyden NA, Bahlmann F, Ravens S, Schubert U, Schmid J, Ludwig S, Geissler K, Guntinas-Lichius O, von Kaisenberg C, Groten T, Platz A, Naumann R, Ludwig B, Prinz I, Waskow C, Krueger A. Enhanced differentiation of functional human T cells in NSGW41 mice with tissue-specific expression of human interleukin-7. Leukemia. 2021 Dec;35(12):3561-3567. doi: 10.1038/s41375-021-01259-5. PMID: 33976371; PMCID: PMC8632686.
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Leukemia. 2021 Dec;35(12):3561-3567. doi: 10.1038/s41375-021-01259-5.

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

Leukemia

Emilie Coppin, Bala Sai Sundarasetty, Susann Rahmig, Jonas Blume, Nikita A Verheyden, Franz Bahlmann, Sarina Ravens, Undine Schubert, Janine Schmid, Stefan Ludwig, Katharina Geissler, Orlando Guntinas-Lichius, Constantin von Kaisenberg, Tanja Groten, Alexander Platz, Ronald Naumann, Barbara Ludwig, Immo Prinz, Claudia Waskow, Andreas Krueger

Affiliations

  1. Regeneration in Hematopoiesis, Institute for Immunology, TU Dresden, Dresden, Germany. [email protected].
  2. Immunology of Aging, Leibniz Institute on Aging-Fritz Lipmann Institute, Jena, Germany. [email protected].
  3. Institute for Molecular Medicine, Goethe University Frankfurt am Main, Frankfurt am Main, Germany.
  4. Recombinant Technologies, CSL Behring GmbH, Marburg, Germany.
  5. Regeneration in Hematopoiesis, Institute for Immunology, TU Dresden, Dresden, Germany.
  6. Immunology of Aging, Leibniz Institute on Aging-Fritz Lipmann Institute, Jena, Germany.
  7. Institute of Immunology, Hannover Medical School, Hannover, Germany.
  8. Department of Obstetrics and Gynecology, Bürgerhospital Frankfurt, Frankfurt am Main, Germany.
  9. Department of Medicine III, Technical University Dresden, Dresden, Germany.
  10. German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany.
  11. Department of Visceral-, Thorax- and Vascular Surgery, Technical University Dresden, Dresden, Germany.
  12. Department of Otorhinolaryngology, Jena University Hospital, Jena, Germany.
  13. Department Obstetrics, Gynecology and Reproductive Medicine, Hannover Medical School, Hannover, Germany.
  14. Department of Obstetrics, Jena University Hospital, Jena, Germany.
  15. DKMS Cord Blood Bank, Dresden, Germany.
  16. Max-Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
  17. Regeneration in Hematopoiesis, Institute for Immunology, TU Dresden, Dresden, Germany. [email protected].
  18. Immunology of Aging, Leibniz Institute on Aging-Fritz Lipmann Institute, Jena, Germany. [email protected].
  19. Department of Medicine III, Technical University Dresden, Dresden, Germany. [email protected].
  20. Faculty of Biological Sciences, Institute of Biochemistry and Biophysics, Friedrich-Schiller-University Jena, Jena, Germany. [email protected].
  21. Institute for Molecular Medicine, Goethe University Frankfurt am Main, Frankfurt am Main, Germany. [email protected].

PMID: 33976371 PMCID: PMC8632686 DOI: 10.1038/s41375-021-01259-5

Abstract

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.

© 2021. The Author(s).

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