Kannagi Mari, Hasegawa Atsuhiko, Takamori Ayako, Kinpara Shuichi, Utsunomiya Atae
Department of Immunotherapeutics, Graduate School, Tokyo Medical and Dental University Tokyo, Japan.
Front Microbiol. 2012 Sep 3;3:323. doi: 10.3389/fmicb.2012.00323. eCollection 2012.
Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis in small subsets of HTLV-1 carriers. HTLV-1-specific T-cell responses play critical roles in anti-viral and anti-tumor host defense during HTLV-1 infections. Some HTLV-1 carriers exhibit selective loss or anergy of HTLV-1-specific T-cells at an asymptomatic stage. This is also observed in ATL patients and may therefore be an underlying risk factor of ATL in combination with elevated proviral loads. HTLV-1-specific T-cells often recognize the viral oncoprotein Tax, indicating expression of Tax protein in vivo, although levels of HTLV-1 gene expression are known to be very low. A type-I interferon (IFN) response can be induced by HTLV-1-infected cells and suppresses HTLV-1 expression in vitro, suggesting a role of type-I IFN response in viral suppression and pathogenesis in vivo. Both acquired and innate immune responses control the status of HTLV-1-infected cells and could be the important determinants in the development of HTLV-1-mediated malignant and inflammatory diseases.
1型人类T细胞白血病病毒(HTLV-1)在一小部分HTLV-1携带者中会引发成人T细胞白血病(ATL)和HTLV-1相关脊髓病/热带痉挛性截瘫。HTLV-1特异性T细胞反应在HTLV-1感染期间的抗病毒和抗肿瘤宿主防御中发挥关键作用。一些HTLV-1携带者在无症状阶段表现出HTLV-1特异性T细胞的选择性丧失或无反应性。这在ATL患者中也有观察到,因此可能是与前病毒载量升高相结合的ATL潜在危险因素。HTLV-1特异性T细胞通常识别病毒癌蛋白Tax,这表明Tax蛋白在体内有表达,尽管已知HTLV-1基因表达水平非常低。1型干扰素(IFN)反应可由HTLV-1感染的细胞诱导,并在体外抑制HTLV-1表达,提示1型干扰素反应在体内病毒抑制和发病机制中发挥作用。获得性免疫反应和先天性免疫反应都控制着HTLV-1感染细胞的状态,并且可能是HTLV-1介导的恶性和炎症性疾病发展的重要决定因素。