The clonal expansion of human T lymphotropic virus type 1-infected T cells: A comparison between seroconverters and long-term carriers

The clonal expansion of human T lymphotropic virus type 1-infected T cells: A comparison between seroconverters and long-term carriers
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DOI:
10.1086/428625
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发表时间:
2005-04-01
影响因子:
6.4
通讯作者:
Tsubouchi, H
Tsubouchi, H
中科院分区:
医学2区
文献类型:
--
作者:
Tanaka, G;Okayama, A;Tsubouchi, H

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背景资料。人类嗜T淋巴细胞病毒1型(HTLV-1)感染的T细胞的克隆性扩增被认为是维持感染的重要因素。然而,HTLV-1感染T细胞的克隆性建立过程尚不清楚。采用反相长链聚合酶链式反应(RT-PCR)分析4例成人血清转换者HTLV-1的克隆性,并对扩增产物进行克隆和限制性内切酶片段长度多态性分析。并与8例HTLV-1长期携带者的检测结果进行比较。血清转换者中感染HTLV-1的T细胞的克隆性是随机上升的,在血清转换后3-5年内是可变的。根据感染HTLV-1前病毒整合位点的细胞克隆出现的频率,可以明显看出,与长期携带者相比,血清转换者拥有更多的独特克隆,感染细胞更少。新近通过HTLV-1携带者配偶感染的成年血清转换者中感染HTLV-1的T细胞的克隆性比长期携带者中感染HTLV-1的T细胞的克隆性更不均匀和不稳定,后者更有可能在婴儿时期感染。在无症状HTLV-1携带者中选择性维持某些克隆的机制可能在白血病发生的启动中起作用。
Background. The clonal expansion of human T lymphotropic virus type 1 (HTLV-1)-infected T cells is considered to be important for the maintenance of infection. However, the process by which the clonality of HTLV-1 -infected T cells is established is not understood.Methods. HTLV-1 clonality in 4 adult seroconverters was analyzed by inverse long polymerase chain reaction (PCR) followed by cloning of the PCR products and evaluation of restriction fragment - length polymorphism. The results were compared with those for 8 long-term HTLV-1 carriers.Results. The clonality of HTLV-1 - infected T cells in the seroconverters arose stochastically and was variable 3 - 5 years after seroconversion. On the basis of the frequency with which clones of cells infected with unique HTLV-1 provirus integration sites appeared, it was clear that the seroconverters had a greater number of unique clones with fewer infected cells than did the long-term carriers.Conclusions. The clonality of the HTLV-1 - infected T cells in the adult seroconverters, who had been newly infected via HTLV-1 - carrier spouses, was more heterogeneous and less stable than that of the HTLV-1 - infected T cells in long-term carriers, who were more likely to have been infected during infancy. The mechanism for the selective maintenance of certain clones in asymptomatic HTLV-1 carriers likely plays a role in the initiation of leukemogenesis.