Neuroimmunological aspects of human T cell leukemia virus type 1- associated myelopathy/tropical spastic paraparesis.
Neuroimmunological aspects of human T cell leukemia virus type 1- associated myelopathy/tropical spastic paraparesis.
复制标题
人类 T 细胞白血病病毒 1 型相关脊髓病/热带痉挛性截瘫的神经免疫学方面。
DOI：
10.1007/s13365-013-0192-8
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发表时间：
2014
期刊：
影响因子：
3.2
通讯作者：
Saito M.
中科院分区：
文献类型：
--
作者：
Tanaka Y;Takahashi Y;Tanaka R;Kodama A;Fujii H;Hasegawa A;Kannagi M;Ansari AA;Saito M.;Saito M.
人类T细胞白血病病毒1型（HTLV-1）是一种具有复制能力的人类逆转录病毒，与两种不同类型的疾病相关：成熟CD 4 + T细胞的恶性肿瘤，称为成人T细胞白血病/淋巴瘤（ATL）。（Hinuma等人，1981年; Poiesz等人，1980年; Yoshida et al. 1984）和慢性炎症性中枢神经系统疾病HTLV-1相关脊髓病/热带痉挛性下肢轻瘫（HAM/TSP）（Gessain等，1985; Osame等，1986）。与人类免疫缺陷病毒（HIV）一样，HTLV-1尽管有强烈的细胞和体液免疫应答，但从未从宿主中消除。然而，与HIV感染相反，很少有HTLV-1感染者发生疾病;只有大约2-3%的感染者发生ATL（Tajima 1990），另外0.25-4%发展为HAM/TSP（Hisada et al. 2004;克雷默et al. 1995; Nakagawa et al. 1995; Osame et al. 1990），并且大多数感染个体保持终身无症状携带者（AC）。因此，评估AC中发生疾病的个体风险肯定是相当重要的，特别是在HTLV-1流行地区。病毒、宿主和环境风险因素以及针对HTLV-1感染的宿主免疫应答似乎调节HTLV-1相关疾病的发生（Bangham和Osame 2005）。特别是，在HAM/TSP患者中观察到对HTLV-1的强烈免疫应答，尤其是细胞毒性T淋巴细胞（CTL）应答，并表明与HTLV-1相关疾病的发病机制密切相关（Matsuura et al. 2010; Saito et al. 2012）。二十多年来，HTLV-1介导的免疫发病机制的研究一直集中在Tax上，这是一种HTLV-1编码的病毒癌蛋白，因为Tax通过与转录因子和辅激活因子结合来激活许多细胞基因，并且对于细胞转化是必要的和足够的。然而，最近的报道已经确定另一种调节蛋白，HTLV-1碱性亮氨酸拉链因子（HBZ），在ATL和HAM/TSP的发展中也具有关键作用（Matsuoka和Jeang 2011）。本文综述了HAM/TSP的过去和最近的研究，试图回答以下基本问题：为什么一些HTLV-1感染的人发展疾病，而绝大多数保持健康？HTLV-1是如何在宿主免疫反应强烈的情况下在个体宿主中持续存在的？HAM/TSP的炎性病变是如何发生和维持的？
Human T cell leukemia virus type 1 (HTLV-1) is a replicationcompetent human retrovirus associated with two distinct types of disease: a malignancy of mature CD4+ T cells called adult T cell leukemia/lymphoma (ATL)(Hinuma et al. 1981; Poiesz et al. 1980; Yoshida et al. 1984) and a chronic inflammatory central nervous system disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP)(Gessain et al. 1985; Osame et al. 1986). Like human immunodeficiency virus (HIV), HTLV-1 is never eliminated from the host despite vigorous cellular and humoral immune responses. However, in contrast to HIV infection, few with HTLV-1 develop disease; only approximately 2–3% of infected persons develop ATL (Tajima 1990), another 0.25–4% develop HAM/TSP (Hisada et al. 2004; Kramer et al. 1995; Nakagawa et al. 1995; Osame et al. 1990), and the majority of infected individuals remain lifelong asymptomatic carriers (ACs). Therefore, evaluation of the individual risk of developing disease in ACs would certainly be of considerable importance, especially in HTLV-1 endemic areas.The viral, host, and environmental risk factors as well as the host immune response against HTLV-1 infection appear to regulate the development of HTLV-1-associated diseases (Bangham and Osame 2005). In particular, a strong immune response, especially the cytotoxic T lymphocyte (CTL) response, to HTLV-1 is seen in patients with HAM/TSP and suggested to be strongly associated with the pathogenesis of HTLV-1-associated diseases (Matsuura et al. 2010; Saito et al. 2012). For more than two decades, the investigation of HTLV-1-mediated immunopathogenesis has focused on Tax, an HTLV-1-encoded viral oncoprotein, because Tax activates many cellular genes by binding to groups of transcription factors and coactivators and is necessary and sufficient for cellular transformation. However, recent reports have identified that another regulatory protein, HTLV-1 basic leucine zipper factor (HBZ), also has a critical role in the development of ATL and HAM/TSP (Matsuoka and Jeang 2011). This review summarizes past and recent studies of HAM/TSP, attempting to answer the following fundamental questions: Why do some HTLV-1-infected people develop disease whereas the vast majority remain healthy? How does HTLV-1 persist in the individual host despite a strong host immune response? How is the inflammatory lesion in HAM/TSP initiated and maintained?