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

Eur J Immunol. 2019 Jun;49(6):954-965. doi: 10.1002/eji.201848001. Epub 2019 Apr 2.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology
  • Cell Differentiation / immunology
  • Disease Models, Animal*
  • HLA-A2 Antigen / genetics
  • HLA-A2 Antigen / immunology
  • HLA-DR2 Antigen / genetics
  • HLA-DR2 Antigen / immunology
  • Humans
  • Lymphopoiesis / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Transgenic*
  • T-Lymphocytes* / cytology
  • T-Lymphocytes* / immunology


  • HLA-A2 Antigen
  • HLA-DR2 Antigen