Significant NK cell activation associated with decreased cytolytic function in peripheral blood of HIV-1-infected patients
Significant NK cell activation associated with decreased cytolytic function in peripheral blood of HIV-1-infected patients
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DOI：
10.1002/eji.200425251
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发表时间：
2004-08-01
影响因子：
5.4
通讯作者：
De Maria, A
中科院分区：
文献类型：
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作者：
Fogli, M;Costa, P;De Maria, A
HIV-1 感染的标志之一是在感染患者的外周血淋巴细胞中发现大量 T 细胞激活。还检测到 HIV-1 感染期间 NK 细胞功能受损，并且与天然细胞毒性受体 (NCR) 表达减少相关。在这项研究中，我们试图确定 NK 细胞是否也受到相关激活的影响，以及这是否可能与 NK 细胞功能下降有关。在 18 名病毒血症 HIV-1 感染患者中，新抽取的纯化外周 NK 细胞显示出显着水平的激活，且模式不完整 (HLA-DR(+)CD69(+)CD25(-)NKp44(-)）。通过细胞荧光分析确定，所有患者的激活的 (HLA-DR(+)CD69(+)) 外周 NK 细胞表达 NCRdull 表型，并且根据 HLA 特异性抑制性 NK 细胞受体的表达分析，并非源自体内同质/寡克隆扩增。细胞毒性测定表明，HIV-1 感染患者中活化的 NK 细胞显示出细胞溶解功能下降。因此，HIV-1感染期间观察到的NK细胞功能下降不仅与NCR表达下降有关，而且与体内NK细胞显着且不完全的激活有关。这些结果表明，先天免疫反应始终持续参与未能控制病毒复制的过程。
One of the hallmarks of HIV-1 infection is represented by the finding of massive T cell activation in peripheral blood lymphocytes of infected patients. An impairment of NK cell function during HIV-1 infection is also detected, and is associated with decreased expression of natural cytotoxicity receptors (NCR). In this study we tried to determine whether also NK cells are affected by relevant activation and whether this could be associated with decreased NK cell function. In 18 viremic HIV-1-infected patients, freshly drawn purified peripheral NK cells displayed significant levels of activation with an incomplete pattern (HLA-DR(+)CD69(+)CD25(-)NKp44(-)). Activated (HLA-DR(+)CD69(+)) peripheral NK cells expressed an NCRdull phenotype as determined by cytofluorometric analysis in all the patients, and did not derive from a homogeneous/oligoclonal expansion in vivo as analyzed by expression of HLA-specific inhibitory NK cell receptors. As determined by cytotoxicity assays, activated NK cells showed a decreased cytolytic function in HIV-1-infected patients. Thus, the decrease in NK cell function observed during HIV-1 infection is associated not only with decreased NCR expression, but also with significant and incomplete NK cell activation in vivo. These results suggest a consistent continuous involvement of the innate immune response in the failure to control viral replication.