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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >In vivo T lymphocyte dynamics in humans and the impact of human T-lymphotropic virus 1 infection
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In vivo T lymphocyte dynamics in humans and the impact of human T-lymphotropic virus 1 infection

机译：人体内T淋巴细胞动力学及其对人T淋巴细胞病毒1感染的影响

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摘要

Human T-lymphotropic virus type 1 (HTLV-1) is a persistent CD4~+ T-lymphotropic retrovirus. Most HTLV-1-infected individuals remain asymptomatic, but a proportion develop adult T cell leukemia or inflammatory disease. It is not fully understood how HTLV-1 persists despite a strong immune response or what determines the risk of HTLV-1-associated diseases. Until recently, it has been difficult to quantify lymphocyte kinetics in humans in vivo. Here, we used deuterated glucose labeling to quantify in vivo lymphocyte dynamics in HTLV-1-infected individuals. We then used these results to address four questions. (ⅰ) What is the impact of HTLV-1 infection on lymphocyte dynamics? (ⅱ) How does HTLV-1 persist? (ⅲ) What is the extent of HTLV-1 expression in vivo? (ⅳ) What features of lymphocyte kinetics are associated with HTLV-1-associated myelopathy/tropical spastic paraparesis? We found that CD4~+CD45RO~+ and CD8~+CD45RO~+ T lymphocyte proliferation was elevated in HTLV-1-infected subjects compared with controls, with an extra 10~(12) lymphocytes produced per year in an HTLV-1-infected subject. The in vivo proliferation rate of CD4~+CD45RO~+ cells also correlated with ex vivo viral expression. Finally, the inflammatory disease HTLV-1-associated myelopathy/tropical spastic paraparesis was associated with significantly increased CD4~+CD45RO~+ cell proliferation. We suggest that there is persistent viral gene expression in vivo, which is necessary for the maintenance of the proviral load and determines HTLV-1-associated myelopathy/tropical spastic paraparesis risk.
机译：1型人类T淋巴病毒（HTLV-1）是一种持久性CD4〜+ T淋巴逆转录病毒。多数感染HTLV-1的个体无症状，但有一部分患上成人T细胞白血病或炎性疾病。尽管有强烈的免疫反应，还是不能确定HTLV-1如何持续存在，还是什么决定了HTLV-1相关疾病的风险，这一点尚不完全清楚。直到最近，还难以量化人体中的淋巴细胞动力学。在这里，我们使用氘化葡萄糖标记来量化HTLV-1感染个体的体内淋巴细胞动力学。然后，我们使用这些结果来解决四个问题。 （ⅰ）HTLV-1感染对淋巴细胞动力学有什么影响？ （ⅱ）HTLV-1如何持续存在？ （ⅲ）HTLV-1在体内的表达程度如何？ （ⅳ）与HTLV-1相关的脊髓病/热带痉挛性轻瘫相比，淋巴细胞动力学有哪些特征？我们发现与对照组相比，HTLV-1感染者的CD4〜+ CD45RO〜+和CD8〜+ CD45RO〜+ T淋巴细胞增殖增加，而HTLV-1每年产生10〜（12）个淋巴细胞。被感染的对象。 CD4〜+ CD45RO〜+细胞的体内增殖率也与离体病毒表达有关。最后，炎性疾病HTLV-1相关的脊髓病/热带痉挛性轻瘫与CD4〜+ CD45RO〜+细胞增殖明显增加有关。我们建议体内存在持续的病毒基因表达，这对于维持前病毒载量和确定HTLV-1相关性脊髓病/热带痉挛性轻瘫的风险是必需的。

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