CD4 and CD8 T cell immune activation during chronic HIV infection: roles of homeostasis, HIV, type I IFN, and IL-7.
CD4 and CD8 T cell immune activation during chronic HIV infection: roles of homeostasis, HIV, type I IFN, and IL-7.
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DOI：
10.4049/jimmunol.1002000
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发表时间：
2011-02-15
期刊：
影响因子：
--
通讯作者：
Lane C
中科院分区：
文献类型：
--
作者：
Catalfamo M;Wilhelm C;Tcheung L;Proschan M;Friesen T;Park JH;Adelsberger J;Baseler M;Maldarelli F;Davey R;Roby G;Rehm C;Lane C
免疫激活在HIV疾病的发病机制中起着重要作用。虽然原因还不完全清楚，但导致免疫功能障碍的力量对于CD 4和CD 8 T细胞是不同的。在这项研究中，我们报告了在慢性HIV感染期间驱动免疫激活的分子途径受到CD 4和CD 8 T细胞库稳态调节差异的影响。CD 4 T细胞的增殖受CD 4 T细胞数量的控制比CD 8 T细胞增殖更严格。这种差异反映了在宿主监测中维持多克隆CD 4 T细胞库的重要性。发现两个T细胞池都是由病毒载量及其相关的炎症状态驱动的。在HIV诱导的淋巴细胞减少症的情况下，初始CD 4 T细胞主要响应于CD 4 T细胞耗竭而被募集到增殖池中，而初始CD 8 T细胞增殖主要由HIV RNA水平驱动。RNA分析显示，在CD 4 T细胞亚群中与I型IFN和常见γ链细胞因子信号传导相关的基因表达增加，而在CD 8 T细胞亚群中仅I型IFN相关基因表达增加。体外研究表明，与在CD 8 T细胞中观察到的相比，初始和记忆CD 4 T细胞中对IFN-α的应答增强了STAT 1磷酸化，并增加了IFNAR 1转录物的表达。CD 4 T细胞亚群也表现出响应于外源性IL-7的增强的STAT 1磷酸化。
Immune activation plays an important role in the pathogenesis of HIV disease. Although the causes are not fully understood, the forces that lead to immune dysfunction differ for CD4 and CD8 T cells. In this study, we report that the molecular pathways that drive immune activation during chronic HIV infection are influenced by differences in the homeostatic regulation of the CD4 and CD8 T cell pools. Proliferation of CD4 T cells is controlled more tightly by CD4 T cell numbers than is CD8 T cell proliferation. This difference reflects the importance of maintaining a polyclonal CD4 T cell pool in host surveillance. Both pools of T cells were found to be driven by viral load and its associated state of inflammation. In the setting of HIV-induced lymphopenia, naive CD4 T cells were recruited mainly into the proliferating pool in response to CD4 T cell depletion, whereas naive CD8 T cell proliferation was driven mainly by levels of HIV RNA. RNA analysis revealed increased expression of genes associated with type I IFN and common γ chain cytokine signaling in CD4 T cell subsets and only type I IFN-associated genes in CD8 T cell subsets. In vitro studies demonstrated enhanced STAT1 phosphorylation in response to IFN-α and increased expression of the IFNAR1 transcripts in naive and memory CD4 T cells compared with that observed in CD8 T cells. CD4 T cell subsets also showed enhanced STAT1 phosphorylation in response to exogenous IL-7.
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TSLP和IL-7使用两种不同的机制来调节人CD4+ T细胞稳态。
影响因子：
15.3
作者：
Lu, Ning;Wang, Yi-Hong;Wang, Yui-Hsi;Arima, Kazuhiko;Hanabuchi, Shino;Liu, Yong-Jun
通讯作者：
Liu, Yong-Jun
影响因子：
3.8
作者：
Phillips, Andrew N.;Lampe, Fiona C.;Johnson, Margaret A.
通讯作者：
Johnson, Margaret A.
影响因子：
6.4
作者：
Lempicki, RA;Polis, MA;Kottilil, S
通讯作者：
Kottilil, S
DOI：
10.1073/pnas.0505251102
发表时间：
2005-09-27
影响因子：
11.1
作者：
Herbeuval, JP;Hardy, AW;Shearer, GM
通讯作者：
Shearer, GM
影响因子：
15.8
作者：
Kuller LH;Tracy R;Belloso W;De Wit S;Drummond F;Lane HC;Ledergerber B;Lundgren J;Neuhaus J;Nixon D;Paton NI;Neaton JD;INSIGHT SMART Study Group
通讯作者：
INSIGHT SMART Study Group