Expansion of human T-cell leukemia virus type 1 (HTLV-1) reservoir in orally infected rats: Inverse correlation with HTLV-1-specific cellular immune response
Expansion of human T-cell leukemia virus type 1 (HTLV-1) reservoir in orally infected rats: Inverse correlation with HTLV-1-specific cellular immune response
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DOI：
10.1128/jvi.77.5.2956-2963.2003
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发表时间：
2003-03-01
影响因子：
5.4
通讯作者：
Kannagi, M
中科院分区：
文献类型：
--
作者：
Hasegawa, A;Ohashi, T;Kannagi, M
成人 T 细胞白血病 (ATL) 发生在一小部分人类 T 细胞白血病病毒 1 型 (HTLV-1) 感染个体中。尽管 ATL 发生的关键危险因素尚不清楚，但人们注意到，ATL 与母婴感染、原病毒载量升高和 HTLV-1 特异性 T 细胞免疫反应减弱有关。在本研究中，我们使用大鼠系统研究了以下条件之间的关系：原发性 HTLV-1 感染、持续的 HTLV-1 负荷和宿主 HTLV-1 特异性免疫。我们发现，经口感染的大鼠体内的持续HTLV-1负荷显着高于腹腔内感染的大鼠。即使只接种了 50 个感染细胞，一些经口感染的大鼠体内的持续病毒载量也达到了相当高的水平，但腹膜内感染的大鼠中则不然。相比之下，口服感染的大鼠中 HTLV-1 特异性细胞免疫反应明显受损。因此，这些大鼠中持续的病毒载量与病毒特异性 T 细胞反应水平呈负相关。另外，经口感染的大鼠中非常弱的HTLV-1特异性细胞免疫反应在用受感染的同基因大鼠细胞皮下再免疫后显着增强。这些发现表明，与口服 HTLV-1 感染相关的 HTLV-1 特异性免疫无反应可能是 ATL 发展的潜在危险因素，允许受感染细胞库在体内扩张，但可以通过免疫策略来克服。
Adult T-cell leukemia (ATL) occurs in a small population of human T-cell leukemia virus type 1 (HTLV-1)-infected individuals. Although the critical risk factor for ATL development is not clear, it has been noted that ATL is incidentally associated with mother-to-child infection, elevated proviral loads, and weakness in HTLV-1-specific T-cell immune responses. In the present study, using a rat system, we investigated the relationships among the following conditions: primary HTLV-1 infection, a persistent HTLV-1 load, and host HTLV-1-specific immunity. We found that the persistent HTLV-1 load in orally infected rats was significantly greater than that in intraperitoneally infected rats. Even after inoculation with only 50 infected cells, a persistent viral load built up to considerable levels in some orally infected rats but not in intraperitoneally infected rats. In contrast, HTLV-1-specific cellular immune responses were markedly impaired in orally, infected rats. As a result, a persistent viral load was inversely correlated with levels of virus-specific T-cell responses in these rats. Otherwise very weak HTLV-1-specific cellular immune responses in orally infected rats were markedly augmented after subcutaneous reimmunization with infected syngeneic rat cells. These findings suggest that HTLV-1-specific immune unresponsiveness associated with oral HTLV-1 infection may be a potential risk factor for development of ATL, allowing expansion of the infected cell reservoir in vivo, but could be overcome with immunological strategies.