論文種別	原著(症例報告除く)
言語種別	英語
査読の有無	その他(不明)
表題	An HTLV-1-Infected Humanized Mouse Model Expressing HLA-A*02:01 Demonstrates Effective CTL-Mediated Suppression of HTLV-1.
掲載誌名	正式名：Viruses 略　 称：Viruses ISSNコード：19994915/19994915
掲載区分	国外
巻・号・頁	17(9),pp.1249
著者・共著者	Shinsuke Nakajima, Motohito Goto, Sung-Il Lee, Tokifumi Odaka, Masaki Hino, Kenta Tezuka, Norihiro Takenouchi, Takaharu Ueno, Fhahira Rizkhika Admadiani, Riichi Takahashi, Isao Hamaguchi, Takeshi Takahashi, Mamoru Ito, Kazu Okuma
発行年月	2025/09
概要	Human T-cell leukemia virus type 1 (HTLV-1) establishes lifelong infection and is associated with severe diseases such as adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Cytotoxic T lymphocytes (CTLs), especially those specific for the viral protein Tax, play a pivotal role in controlling HTLV-1 infection. However, conventional humanized mouse models fail to fully reconstitute human immune responses, limiting their utility for evaluating CTL-mediated immunity. This study aimed to establish a physiologically relevant in vivo model to investigate human CTL responses against HTLV-1. To achieve this, we utilized NOG-HLA-A02 transgenic (Tg) mice expressing human HLA-A02:01 on thymic epithelial cells, enabling proper development of HLA-restricted human T cells. Compared to conventional humanized NOG mice, HTLV-1-infected humanized NOG-HLA-A02 Tg mice exhibited significantly reduced HTLV-1 proviral load (PVL), decreased expansion of infected CD4+ T cells, a trend toward increased frequencies of Tax-specific CD8+ T cells, and prolonged survival. These results demonstrate that the expression of HLA-A02:01 facilitates robust CTL-mediated immune control of HTLV-1. This model provides a powerful platform for dissecting HTLV-1 immunopathogenesis and evaluating CTL-targeted therapeutic strategies, including vaccines and immune checkpoint inhibitors.
DOI	10.3390/v17091249
PMID	41012676