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

Guillemette Masse-Ranson; Mathilde Dusseaux; Oriane Fiquet; Sylvie Darche; Maud Boussand; Yan Li; Silvia Lopez-Lastra; Nicolas Legrand; Erwan Corcuff; Antoine Toubert; Mireille Centlivre; Timothée Bruel; Hergen Spits; Olivier Schwartz; Yves Levy; Helene Strick-Marchand; James Di Santo

doi:10.1002/eji.201848001

Journal articles

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

Guillemette Masse-Ranson ^{1, 2} Mathilde Dusseaux ¹ Oriane Fiquet ¹ Sylvie Darche ¹ Maud Boussand ¹ Yan Li ¹ Silvia Lopez-Lastra ¹ Nicolas Legrand Erwan Corcuff Antoine Toubert ^{3, 4, 5} Mireille Centlivre ² Timothée Bruel ^{6, 2} Hergen Spits ⁷ Olivier Schwartz ^{6, 2} Yves Levy ^{2, 8, 9} Helene Strick-Marchand ¹ James Di Santo ^{1, *}

* Corresponding author

1 Immunité Innée

2 VRI - Vaccine Research Institute

3 Service d'Immunologie et d'Histocompatibilité

4 IUH - Institut Universitaire d'Hématologie

5 EMily (UMR_S_1160 / U1160) - Ecotaxie, microenvironnement et développement lymphocytaire

6 Virus et Immunité

7 AMC - Academic Medical Center - Academisch Medisch Centrum [Amsterdam]

8 IMRB - Institut Mondor de Recherche Biomédicale

9 Service d'immunologie clinique et maladies infectieuses [Créteil]

Groupe Henri Mondor-Albert Chenevier

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.

Keywords : Animal models Humanized mice Lymphocyte development

Document type :

Journal articles

Domain :

Life Sciences [q-bio] / Immunology / Adaptive immunology

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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 : Monday, December 14, 2020 - 3:41:00 PM

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

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

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