{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T08:31:48Z","timestamp":1774945908173,"version":"3.50.1"},"reference-count":40,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2023,7,20]],"date-time":"2023-07-20T00:00:00Z","timestamp":1689811200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Kansai Medical University","doi-asserted-by":"publisher","award":["20K17036"],"award-info":[{"award-number":["20K17036"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Kansai Medical University","doi-asserted-by":"publisher","award":["20K17036"],"award-info":[{"award-number":["20K17036"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Institute for Enzyme Research Joint Usage\/Research Center, Tokushima University","doi-asserted-by":"publisher","award":["20K17036"],"award-info":[{"award-number":["20K17036"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Institute for Enzyme Research Joint Usage\/Research Center, Tokushima University","doi-asserted-by":"publisher","award":["20K17036"],"award-info":[{"award-number":["20K17036"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Immune responses in humanized mice are generally inefficient without co-transplantation of human thymus or HLA transgenes. Previously, we generated humanized mice via the intra-bone marrow injection of CD133+ cord blood cells into irradiated adult immunodeficient mice (IBMI-huNSG mice), which could mount functional immune responses against HTLV-1, although the underlying mechanisms were still unknown. Here, we investigated thymocyte development in IBMI-huNSG mice, focusing on the roles of human and mouse MHC restriction. IBMI-huNSG mice had normal developmental profiles but aberrant thymic structures. Surprisingly, the thymic medulla-like regions expanded after immunization due to enhanced thymocyte expansion in association with the increase in HLA-DR+ cells, including CD205+ dendritic cells (DCs). The organ culture of thymus from immunized IBMI-huNSG mice with a neutralizing antibody to HLA-DR showed the HLA-DR-dependent expansion of CD4 single positive thymocytes. Mature peripheral T-cells exhibited alloreactive proliferation when co-cultured with human peripheral blood mononuclear cells. Live imaging of the thymus from immunized IBMI-huNSG mice revealed dynamic adhesive contacts of human-derived thymocytes and DCs accompanied by Rap1 activation. These findings demonstrate that an increase in HLA-DR+ cells by immunization promotes HLA-restricted thymocyte expansion in humanized mice, offering a unique opportunity to generate humanized mice with ease.<\/jats:p>","DOI":"10.3390\/ijms241411705","type":"journal-article","created":{"date-parts":[[2023,7,21]],"date-time":"2023-07-21T01:52:35Z","timestamp":1689904355000},"page":"11705","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Thymocyte Development of Humanized Mice Is Promoted by Interactions with Human-Derived Antigen Presenting Cells upon Immunization"],"prefix":"10.3390","volume":"24","author":[{"given":"Takataro","family":"Fukuhara","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology, The Third Department of Internal Medicine, Kansai Medical University, Hirakata 573-1010, Osaka, Japan"},{"name":"Department of Molecular Genetics, Institute of Biomedical Science, Kansai Medical University, Hirakata 573-1010, Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1112-9841","authenticated-orcid":false,"given":"Yoshihiro","family":"Ueda","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Institute of Biomedical Science, Kansai Medical University, Hirakata 573-1010, Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sung-Il","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Model Animal, Institute of Biomedical Science, Kansai Medical University, Hirakata 573-1010, Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tokifumi","family":"Odaka","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Kansai Medical University, Hirakata 573-1010, Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinsuke","family":"Nakajima","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Kansai Medical University, Hirakata 573-1010, Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun-Ichi","family":"Fujisawa","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Kansai Medical University, Hirakata 573-1010, Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazu","family":"Okuma","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Kansai Medical University, Hirakata 573-1010, Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Makoto","family":"Naganuma","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, The Third Department of Internal Medicine, Kansai Medical University, Hirakata 573-1010, Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuichi","family":"Okazaki","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, The Third Department of Internal Medicine, Kansai Medical University, Hirakata 573-1010, Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6624-5989","authenticated-orcid":false,"given":"Naoyuki","family":"Kondo","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Institute of Biomedical Science, Kansai Medical University, Hirakata 573-1010, Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7532-1787","authenticated-orcid":false,"given":"Yuji","family":"Kamioka","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Institute of Biomedical Science, Kansai Medical University, Hirakata 573-1010, Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitsuru","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Division of Molecular Immunology, Institute for Enzyme Research, Tokushima University, Kuramoto 770-8503, Tokushima, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatsuo","family":"Kinashi","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Institute of Biomedical Science, Kansai Medical University, Hirakata 573-1010, Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3723","DOI":"10.1002\/jcp.26045","article-title":"Humanized mouse models: Application to human diseases","volume":"233","author":"Ito","year":"2018","journal-title":"J. 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