In vivo T lymphocyte dynamics in humans and the impact of human T-lymphotropic virus 1 infection
In vivo T lymphocyte dynamics in humans and the impact of human T-lymphotropic virus 1 infection
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DOI：
10.1073/pnas.0608832104
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发表时间：
2007-05-08
影响因子：
11.1
通讯作者：
Bangham, Charles R. M.
中科院分区：
文献类型：
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作者：
Asquith, Becca;Zhang, Yan;Bangham, Charles R. M.
人嗜T细胞病毒1型(HTLV-1)是一种持续存在的CD4(+)嗜T细胞逆转录病毒。大多数感染HTLV-1的人仍然没有症状，但也有一部分人发展为成人T细胞白血病或炎症性疾病。尽管有强烈的免疫反应，但HTLV-1如何持续存在，以及是什么决定了HTLV-1相关疾病的风险，目前尚不完全清楚。直到最近，还很难量化活体内人类的淋巴细胞动力学。在这里，我们使用氚葡萄糖标记来量化体内HTLV-1感染个体的淋巴细胞动力学。然后，我们利用这些结果回答了四个问题。(I)HTLV-1感染对淋巴细胞动力学有何影响？(IT)HTLV-1是如何持续的？(3)HTLV-1在体内的表达程度如何？(Iv)淋巴细胞动力学的哪些特征与HTLV-1相关性脊髓病/热带痉挛截瘫有关？我们发现，与对照组相比，HTLV-1感染者的CD4(+)CD45RO(+)和CD8(+)CD45RO(+)T淋巴细胞的增殖率升高，并且每年多产生10(12)个淋巴细胞。CD4(+)CD45RO(+)细胞的体内增殖率也与体外病毒表达有关。最后，炎症性疾病HTLV-1相关性脊髓病/热带痉挛截瘫与显著增加的CD4(+)CD45RO(+)细胞增殖有关。我们认为体内存在持续的病毒基因表达，这是维持前病毒负荷所必需的，并决定了HTLV-1相关性脊髓病/热带痉挛截瘫的风险。
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? (it) 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.