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Accelerated thymopoiesis and improved T‐cell responses in HLA‐A2/‐DR2 transgenic BRGS‐based human immune system mice

Abstract : Human immune system (HIS) mouse models provide a robust in vivo platform to study human immunity. Nevertheless, the signals that guide human lymphocyte differentiation in HIS mice remain poorly understood. Here, we have developed a novel Balb/c Rag2-/- Il2rg-/- SirpaNOD (BRGS) HIS mouse model expressing human HLA-A2 and -DR2 transgenes (BRGSA2DR2). When comparing BRGS and BRGSA2DR2 HIS mice engrafted with human CD34+ stem cells, a more rapid emergence of T cells in the circulation of hosts bearing human HLA was shown, which may reflect a more efficient human T-cell development in the mouse thymus. Development of CD4+ and CD8+ T cells was accelerated in BRGSA2DR2 HIS mice and generated more balanced B and T-cell compartments in peripheral lymphoid organs. Both B- and T-cell function appeared enhanced in the presence of human HLA transgenes with higher levels of class switched Ig, increased percentages of polyfunctional T cells and clear evidence for antigen-specific T-cell responses following immunization. Taken together, the presence of human HLA class I and II molecules can improve multiple aspects of human B- and T-cell homeostasis and function in the BRGS-based HIS mouse model.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-02875581
Contributor : Helene Strick-Marchand <>
Submitted on : Friday, June 19, 2020 - 6:14:15 PM
Last modification on : Wednesday, August 19, 2020 - 11:19:12 AM

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Guillemette Masse-Ranson, Mathilde Dusseaux, Oriane Fiquet, Sylvie Darche, Maud Boussand, et al.. Accelerated thymopoiesis and improved T‐cell responses in HLA‐A2/‐DR2 transgenic BRGS‐based human immune system mice. European Journal of Immunology, Wiley-VCH Verlag, 2019, 49 (6), pp.954-965. ⟨10.1002/eji.201848001⟩. ⟨pasteur-02875581⟩

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