Title |
Enhanced Antibody Responses in a Novel NOG Transgenic Mouse with Restored Lymph Node Organogenesis
|
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Published in |
Frontiers in immunology, January 2018
|
DOI | 10.3389/fimmu.2017.02017 |
Pubmed ID | |
Authors |
Takeshi Takahashi, Ikumi Katano, Ryoji Ito, Motohito Goto, Hayato Abe, Seiya Mizuno, Kenji Kawai, Fumihiro Sugiyama, Mamoru Ito |
Abstract |
Lymph nodes (LNs) are at the center of adaptive immune responses. Various exogenous substances are transported into LNs and a series of immune responses ensue after recognition by antigen-specific lymphocytes. Although humanized mice have been used to reconstitute the human immune system, most lack LNs due to deficiency of the interleukin (IL)-2Rγ gene (cytokine common γ chain, γc). In this study, we established a transgenic strain, NOG-pRORγt-γc, in the NOD/shi-scid-IL-2Rγnull (NOG) background, in which the γc gene was expressed in a lymph-tissue inducer (LTi) lineage by the endogenous promoter of RORγt. In this strain, LN organogenesis was normalized and the number of human T cells substantially increased in the periphery after reconstitution of the human immune system by human hematopoietic stem cell transplantation. The distribution of human T cells differed between NOG-pRORγt-γc Tg and NOG-non Tg mice. About 40% of human T cells resided in LNs, primarily the mesenteric LNs. The LN-complemented humanized mice exhibited antigen-specific immunoglobulin G responses together and an increased number of IL-21+-producing CD4+ T cells in LNs. This novel mouse strain will facilitate recapitulation of human immune responses. |
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