Accelerated thymopoiesis and improved T‐cell responses in HLA‐A2/‐DR2 transgenic BRGS‐based human immune system mice - Institut Pasteur Access content directly
Journal Articles European Journal of Immunology Year : 2019

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

Oriane Fiquet
Yan Li
Silvia Lopez-Lastra
  • Function : Author
  • PersonId : 773706
  • IdRef : 200805878
Nicolas Legrand
  • Function : Author
Erwan Corcuff
  • Function : Author
Helene Strick-Marchand
  • Function : Author
  • PersonId : 1019959

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.

Dates and versions

pasteur-02875581 , version 1 (19-06-2020)

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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, 2019, 49 (6), pp.954-965. ⟨10.1002/eji.201848001⟩. ⟨pasteur-02875581⟩
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