Characterization of programmed death-1 homologue-1 (PD-1H) expression and function in normal and HIV infected individuals.
Characterization of programmed death-1 homologue-1 (PD-1H) expression and function in normal and HIV infected individuals.
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DOI：
10.1371/journal.pone.0109103
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Shankar P
中科院分区：
文献类型：
--
作者：
Bharaj P;Chahar HS;Alozie OK;Rodarte L;Bansal A;Goepfert PA;Dwivedi A;Manjunath N;Shankar P
尽管接受了抗逆转录病毒治疗(ART)，但持续的慢性免疫激活是艾滋病毒感染中疾病进展的最强预测因素。已知HIV感染者的单核/巨噬细胞会自发分泌细胞因子，尽管机制和涉及的分子都不清楚。在这里，我们证明了新描述的共刺激分子PD1同源分子(PD-1H)在人类单核/巨噬细胞中的过度表达足以诱导多种细胞因子的自发分泌。这一过程需要通过PD-1H进行信号传递，因为细胞因子的分泌可以通过胞浆结构域的缺失而被取消。在慢性HIV感染者的单核细胞中可以看到PD-1H的过度表达，与自发的细胞因子表达有关，这与免疫激活和CD4耗尽有关，但与病毒载量无关。此外，PD-1H过表达的单核细胞的抗原呈递导致HIV特异性T细胞分泌细胞因子的增加。这些结果提示，PD-1H可能在调节HIV感染的免疫激活和免疫反应中发挥重要作用。
Chronic immune activation that persists despite anti-retroviral therapy (ART) is the strongest predictor of disease progression in HIV infection. Monocyte/macrophages in HIV-infected individuals are known to spontaneously secrete cytokines, although neither the mechanism nor the molecules involved are known. Here we show that overexpression of the newly described co-stimulatory molecule, PD1 homologue (PD-1H) in human monocyte/macrophages is sufficient to induce spontaneous secretion of multiple cytokines. The process requires signaling via PD-1H as cytokine secretion could be abrogated by deletion of the cytoplasmic domain. Such overexpression of PD-1H, associated with spontaneous cytokine expression is seen in monocytes from chronically HIV-infected individuals and this correlates with immune activation and CD4 depletion, but not viral load. Moreover, antigen presentation by PD-1H-overexpressing monocytes results in enhanced cytokine secretion by HIV-specific T cells. These results suggest that PD-1H might play a crucial role in modulating immune activation and immune response in HIV infection.
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影响因子：
11.2
作者：
Le Mercier I;Chen W;Lines JL;Day M;Li J;Sergent P;Noelle RJ;Wang L
通讯作者：
Wang L
DOI：
10.1084/jem.20100619
发表时间：
2011-03-14
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Wang L;Rubinstein R;Lines JL;Wasiuk A;Ahonen C;Guo Y;Lu LF;Gondek D;Wang Y;Fava RA;Fiser A;Almo S;Noelle RJ
通讯作者：
Noelle RJ
影响因子：
8.7
作者：
Nurieva RI;Liu X;Dong C
通讯作者：
Dong C
影响因子：
4.6
作者：
Hunt, Peter W
通讯作者：
Hunt, Peter W
影响因子：
4.6
作者：
Hunt, Peter W.
通讯作者：
Hunt, Peter W.