TY - JOUR
T1 - Accelerated thymopoiesis and improved T-cell responses in HLA-A2/-DR2 transgenic BRGS-based human immune system mice
AU - Masse-Ranson, Guillemette
AU - Dusséaux, Mathilde
AU - Fiquet, Oriane
AU - Darche, Sylvie
AU - Boussand, Maud
AU - Li, Yan
AU - Lopez-Lastra, Silvia
AU - Legrand, Nicolas
AU - Corcuff, Erwan
AU - Toubert, Antoine
AU - Centlivre, Mireille
AU - Bruel, Timothée
AU - Spits, Hergen
AU - Schwartz, Olivier
AU - Lévy, Yves
AU - Strick-Marchand, H. lène
AU - di Santo, James P.
PY - 2019/6
Y1 - 2019/6
N2 - 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.
AB - 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85063799891&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/30888052
U2 - https://doi.org/10.1002/eji.201848001
DO - https://doi.org/10.1002/eji.201848001
M3 - Article
C2 - 30888052
SN - 0014-2980
VL - 49
SP - 954
EP - 965
JO - European journal of immunology
JF - European journal of immunology
IS - 6
ER -