HIV-1 Nef impairs multiple T-cell functions in antigen-specific immune response in mice
HIV-1 Nef impairs multiple T-cell functions in antigen-specific immune response in mice
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HIV-1 Nef 损害小鼠抗原特异性免疫反应中的多种 T 细胞功能
DOI：
10.1093/intimm/dxr031
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
T.
中科院分区：
文献类型：
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作者：
Fujii;H.;Ato;M.;Takahashi;Y.;Otake;K.;Hashimoto;S.;Kaji;T.;Tsunetsugu-Yokota;Y.;Fujita;M.;Adachi;A.;Nakayama;T.;Taniguchi;M. Koyasu;S.;Takemori;T.
病毒蛋白Nef是艾滋病毒疾病进展的关键因素。先前的体外研究表明，在TCR交联刺激下，Nef在T细胞系中的表达增强了TCR信号通路，导致了Nef降低了T细胞激活的阈值，从而增加了免疫反应中对病毒复制的敏感性。同样，Nef转基因小鼠模型的活体效应支持Nef的T细胞高反应。然而，在这些动物模型中，Nef在T细胞发育早期的表达使解释变得复杂。在这里，我们通过一个新的小鼠模型分析了Nef在卵白蛋白特异性/CD4+外周T细胞中表达的结果，并证明了Nef抑制抗原特异性T细胞的增殖和体内免疫反应所需的多种功能，包括T细胞对初级和记忆性B细胞反应的辅助活性。然而，Nef并不能完全消除T细胞活性，如低水平的细胞因子产生所定义的那样，这可能为病毒提供复制优势。这些结果支持一种模型，在该模型中，Nef的表达不会引起免疫反应中的T细胞高反应，而是降低T细胞的活性，这可能有助于低水平的病毒传播而没有病毒的细胞病变效应。
The viral protein Nef is a key element for the progression of HIV disease. Previousin vitrostudies suggested that Nef expression in T-cell lines enhanced TCR signaling pathways upon stimulation with TCR cross-linking, leading to the proposal that Nef lowers the threshold of T-cell activation, thus increasing susceptibility to viral replication in immune response. Likewise, thein vivoeffects of Nef transgenic mouse models supported T-cell hyperresponse by Nef. However, the interpretation is complicated by Nef expression early in the development of T cells in these animal models. Here, we analyzed the consequence of Nef expression in ovalbumin-specific/CD4+peripheral T cells by using a novel mouse model and demonstrate that Nef inhibits antigen-specific T-cell proliferation and multiple functions required for immune responsein vivo, which includes T-cell helper activity for the primary and memory B-cell response. However, Nef does not completely abrogate T-cell activity, as defined by low levels of cytokine production, which may afford the virus a replicative advantage. These results support a model, in which Nef expression does not cause T-cell hyperresponse in immune reaction, but instead reduces the T-cell activity, that may contribute to a low level of virus spread without viral cytopathic effects.