First Author | Masse-Ranson G | Year | 2019 |
Journal | Eur J Immunol | Volume | 49 |
Issue | 6 | Pages | 954-965 |
PubMed ID | 30888052 | Mgi Jnum | J:277140 |
Mgi Id | MGI:6317141 | Doi | 10.1002/eji.201848001 |
Citation | Masse-Ranson G, et al. (2019) Accelerated thymopoiesis and improved T-cell responses in HLA-A2/-DR2 transgenic BRGS-based human immune system mice. Eur J Immunol 49(6):954-965 |
abstractText | 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(-/-) Sirpa(NOD) (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. |