期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 49, 期 6, 页码 954-965出版社
WILEY
DOI: 10.1002/eji.201848001
关键词
Animal models; Humanized mice; Lymphocyte development
类别
资金
- Institut Pasteur
- INSERM
- Gates Foundation (Grand Challenges in Global Health)
- Agence Nationale de la Recherche (ANR) programme RPIB
- Laboratoire d'Excellence REVIVE [ANR-10-LABX-73]
- Laboratoire d'Excellence Vaccine Research Institute [ANR-10-LABX-77]
- Laboratoire d'Excellence Milieu Interieur [ANR-10-LABX-69]
- Laboratoire d'Excellence IBEID [ANR-10-LABX-62]
- Agence Nationale de Recherche sur le SIDA et les hepatites virales [ANRS 15465]
- European Commission Seventh Framework Programme [305578]
- Gilead Sciences [00397]
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.
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