Leukemia · 2021
Enhanced differentiation of functional human T cells in NSGW41 mice with tissue-specific expression of human interleukin-7.
Письмо в редакциюПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Coppin Emilie, Sundarasetty Bala Sai, Rahmig Susann, Blume Jonas, Verheyden Nikita A, Bahlmann Franz, Ravens Sarina, Schubert Undine, Schmid Janine, Ludwig Stefan, Geissler Katharina, Guntinas-Lichius Orlando, von Kaisenberg Constantin, Groten Tanja, Platz Alexander, Naumann Ronald, Ludwig Barbara, Prinz Immo, Waskow Claudia, Krueger Andreas
Аннотация
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.