Enhanced Antibody Responses in a Novel NOG Transgenic Mouse with Restored Lymph Node Organogenesis
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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2017.02017/full |
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| author | Takeshi Takahashi Ikumi Katano Ryoji Ito Motohito Goto Hayato Abe Seiya Mizuno Kenji Kawai Fumihiro Sugiyama Mamoru Ito |
| author_facet | Takeshi Takahashi Ikumi Katano Ryoji Ito Motohito Goto Hayato Abe Seiya Mizuno Kenji Kawai Fumihiro Sugiyama Mamoru Ito |
| author_sort | Takeshi Takahashi |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T07:15:10Z |
| format | Article |
| id | doaj.art-c3dff4f55ea5488f8eca7e62264a787a |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-11T07:15:10Z |
| publishDate | 2018-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-c3dff4f55ea5488f8eca7e62264a787a2022-12-22T01:16:15ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-01-01810.3389/fimmu.2017.02017316886Enhanced Antibody Responses in a Novel NOG Transgenic Mouse with Restored Lymph Node OrganogenesisTakeshi Takahashi0Ikumi Katano1Ryoji Ito2Motohito Goto3Hayato Abe4Seiya Mizuno5Kenji Kawai6Fumihiro Sugiyama7Mamoru Ito8Central Institute for Experimental Animals, Kawasaki, JapanCentral Institute for Experimental Animals, Kawasaki, JapanCentral Institute for Experimental Animals, Kawasaki, JapanCentral Institute for Experimental Animals, Kawasaki, JapanCentral Institute for Experimental Animals, Kawasaki, JapanLaboratory Animal Resource Center, University of Tsukuba, Tsukuba, JapanCentral Institute for Experimental Animals, Kawasaki, JapanLaboratory Animal Resource Center, University of Tsukuba, Tsukuba, JapanCentral Institute for Experimental Animals, Kawasaki, JapanLymph 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.http://journal.frontiersin.org/article/10.3389/fimmu.2017.02017/fullhumanized miceNOGlymph nodeT cellhomeostasis |
| spellingShingle | Takeshi Takahashi Ikumi Katano Ryoji Ito Motohito Goto Hayato Abe Seiya Mizuno Kenji Kawai Fumihiro Sugiyama Mamoru Ito Enhanced Antibody Responses in a Novel NOG Transgenic Mouse with Restored Lymph Node Organogenesis Frontiers in Immunology humanized mice NOG lymph node T cell homeostasis |
| title | Enhanced Antibody Responses in a Novel NOG Transgenic Mouse with Restored Lymph Node Organogenesis |
| title_full | Enhanced Antibody Responses in a Novel NOG Transgenic Mouse with Restored Lymph Node Organogenesis |
| title_fullStr | Enhanced Antibody Responses in a Novel NOG Transgenic Mouse with Restored Lymph Node Organogenesis |
| title_full_unstemmed | Enhanced Antibody Responses in a Novel NOG Transgenic Mouse with Restored Lymph Node Organogenesis |
| title_short | Enhanced Antibody Responses in a Novel NOG Transgenic Mouse with Restored Lymph Node Organogenesis |
| title_sort | enhanced antibody responses in a novel nog transgenic mouse with restored lymph node organogenesis |
| topic | humanized mice NOG lymph node T cell homeostasis |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2017.02017/full |
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