Impact of Persistent HIV Replication on CD4 Negative Vγ2Vδ2 T Cells
Impact of Persistent HIV Replication on CD4 Negative Vγ2Vδ2 T Cells
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DOI：
10.1093/infdis/jis217
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发表时间：
2012-05-01
影响因子：
6.4
通讯作者：
Pauza, C. David
中科院分区：
文献类型：
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作者：
Boudova, Sarah;Li, Haishan;Pauza, C. David
背景CD 4- V γ 2 V δ 2 T细胞在人类免疫缺陷病毒（HIV）感染期间耗尽，但在没有治疗的情况下自发控制病毒血症的患者中可以恢复到接近正常水平。通过对比V γ 2 V δ 2 T细胞数量、表型和T细胞受体（TCR）库，我们研究了持续性病毒血症期间主动免疫和进行性T细胞破坏之间的动态张力。通过流式细胞术表征外周血V γ 2 V δ 2 T细胞水平和表型。细胞增殖测定测量功能反应。频谱分析表征了TCR库的损伤。持续性病毒血症患者中T效应记忆V γ 2 V δ 2 T细胞的水平、对抗原的应答和比例介于自然病毒抑制（NVS）患者和接受抗逆转录病毒治疗的患者之间。与抗逆转录病毒治疗接受者和自然病毒抑制患者相比，病毒血症患者TCR γ-2链库受损和CD 56 + V γ 2 V δ 2 T细胞耗竭更为明显。病毒血症患者中V γ 2 V δ 2 T细胞的特征反映了主动应答（增加的细胞数量、更好的抗原应答和更高比例的效应记忆细胞）和持续的损伤（库变化和CD 561细胞的损失）。与将病毒血症控制到不可检测水平的患者不同，V γ 2 V δ 2 T细胞在持续性病毒血症期间减少，并且可能最终由于TCR库的进行性破坏而丢失。
Background. CD4- V gamma 2V delta 2 T cells are depleted during human immunodeficiency virus (HIV) infection but can recover to near normal levels in patients who spontaneously control viremia in the absence of therapy. By contrasting V gamma 2V delta 2 T-cell numbers, phenotype, and T-cell receptor (TCR) repertoire, we investigate the dynamic tension between active immunity and progressive T-cell destruction during persistent viremia.Methods. Peripheral blood V gamma 2V delta 2 T-cell levels and phenotypes were characterized by flow cytometry. Lymphoproliferation assays measured functional responses. Spectratyping characterized damage to the TCR repertoire.Results. Levels, responses to antigen and the proportion of T effector memory V gamma 2V delta 2 T cells in patients with persistent viremia, were intermediate between patients with natural virus suppression (NVS) and patients receiving antiretroviral therapy. Damage to the TCR gamma-2 chain repertoire and depletion of CD56+ V gamma 2V delta 2 T cells were more pronounced in viremic patients, compared with antiretroviral therapy recipients and patients with natural virus suppression.Conclusions. Characteristics of V gamma 2V delta 2 T cells in viremic patients reflect both active responses (increasing cell numbers, better antigen responses, and higher proportion of effector memory cells) and ongoing damage (repertoire changes and loss of CD561 cells). Unlike patients who control viremia to undetectable levels, V gamma 2V delta 2 T cells are diminished during persistent viremia and may eventually be lost because of progressive destruction of the TCR repertoire.