AIDS Research Center, National Institute of Infectious Diseases.
Global Virus Network.
Jpn J Infect Dis. 2020 May 22;73(3):221-225. doi: 10.7883/yoken.JJID.2019.494. Epub 2020 Jan 31.
Adult T-cell leukemia (ATL) is induced by chronic latent infection with human T-cell leukemia virus type 1 (HTLV-1). HTLV-1 Tax is an oncogenic factor that can be targeted by host T-cell responses. However, the expression of Tax in vivo is little in ATL cells and the impact of Tax-specific T-cell responses on ATL progression remains unclear. In the present study, we examined Tax-specific T-cell responses in C57BL/6 mice after syngeneic transplantation with tax-transgenic mouse-derived ATL (mATL) cells. We first confirmed that cellular tax cDNAs are mostly maintained and detectable in the spleen three weeks after mATL cell transplantation. However, mATL cell transplantation did not induce significant Tax-specific T-cell responses. Mice immunized with DNA and adenovirus vectors expressing Tax exhibited Tax-specific CD4 T-cell responses but showed no enhancement of the responses or reduction in cellular tax cDNA levels after mATL cell transplantation. This study provides an animal model for analyzing the interaction between ATL cells and host immune responses as well as indicates the limited impact of Tax-specific T-cell responses on the proliferation of ATL cells.
成人 T 细胞白血病（ATL）是由人类 T 细胞白血病病毒 1（HTLV-1）的慢性潜伏感染引起的。HTLV-1 Tax 是一种致癌因子，可以被宿主 T 细胞反应靶向。然而，在体内 ATL 细胞中 Tax 的表达量很少，Tax 特异性 T 细胞反应对 ATL 进展的影响仍不清楚。在本研究中，我们在 C57BL/6 小鼠中检查了 Tax 特异性 T 细胞反应，这些小鼠接受了同种异体移植的 Tax 转基因小鼠源性 ATL（mATL）细胞。我们首先证实，在 mATL 细胞移植后三周，脾脏中细胞 tax cDNA 大多被维持且可检测到。然而，mATL 细胞移植并未诱导明显的 Tax 特异性 T 细胞反应。用表达 Tax 的 DNA 和腺病毒载体免疫的小鼠表现出 Tax 特异性 CD4 T 细胞反应，但在 mATL 细胞移植后，其反应没有增强，细胞 tax cDNA 水平也没有降低。这项研究提供了一个分析 ATL 细胞与宿主免疫反应相互作用的动物模型，并表明 Tax 特异性 T 细胞反应对 ATL 细胞增殖的影响有限。
