Division of Infectious Diseases, Department of Medicine.
Department of Biostatistics and Center for AIDS Research.
AIDS. 2020 Mar 1;34(3):363-371. doi: 10.1097/QAD.0000000000002434.
To study the contribution of γδ T cells to the persistent HIV reservoir.
Fifteen HIV-seropositive individuals on suppressive ART were included. We performed parallel quantitative viral outgrowth assays (QVOA) of resting CD4 T (rCD4) cells in the presence or absence of γδ T cells.
Resting αβ+CD4 T cells were magnetically isolated from PBMCs using two different custom cocktails, only one kit contained antibodies to deplete γδ T cells, resulting in two populations: rCD4 cells and rCD4 cells depleted of γδ cells. Frequency of infection was analyzed by QVOA and DNA measurements.
Recovery of replication-competent HIV from cultures of rCD4 cells was similar in 11 individuals despite the presence of γδ T cells. In four donors, HIV recovery was lower when γδ T cells were present. Expression of the cytotoxic marker CD16 on Vδ2 cells was the only variable associated with the lower HIV recovery. Our results highlight the potency of those responses since a mean of 10 000 γδ T cells were present within 2.5 million rCD4 cells. However, despite the low frequency of γδ T cells, the presence of cytotoxic Vδ2 cells correlated with lower HIV recovery from cultures of rCD4 cells.
Results of this study show that quantification of the contribution of γδ T cells to the reservoir is challenging because of their low numbers compared with conventional rCD4 cells and highlights the potent antiviral function of γδ T cells and the impact of their presence on the frequency of latent HIV infection.
研究 γδ T 细胞对持续性 HIV 储存库的贡献。
纳入了 15 名接受抑制性 ART 的 HIV 血清阳性个体。我们进行了 rCD4 细胞（静息 CD4 T 细胞）在存在或不存在 γδ T 细胞情况下的平行定量病毒扩增测定（QVOA）。
使用两种不同的定制鸡尾酒，通过磁性从 PBMCs 中分离静息 αβ+CD4 T 细胞，只有一个试剂盒包含耗竭 γδ T 细胞的抗体，从而产生两种细胞群：rCD4 细胞和耗竭 γδ 细胞的 rCD4 细胞。通过 QVOA 和 DNA 测量分析感染频率。
尽管存在 γδ T 细胞，但 11 名个体的 rCD4 细胞培养物中复制型 HIV 的恢复情况相似。在四名供体中，当存在 γδ T 细胞时，HIV 恢复较低。Vδ2 细胞上细胞毒性标志物 CD16 的表达是与较低 HIV 恢复相关的唯一变量。我们的结果强调了这些反应的效力，因为在 250 万个 rCD4 细胞中存在平均 10000 个 γδ T 细胞。然而，尽管 γδ T 细胞的频率较低，但存在细胞毒性 Vδ2 细胞与 rCD4 细胞培养物中 HIV 恢复率较低相关。
本研究的结果表明，由于与常规 rCD4 细胞相比，γδ T 细胞数量较少，因此量化 γδ T 细胞对储存库的贡献具有挑战性，并强调了 γδ T 细胞的强大抗病毒功能及其存在对潜伏 HIV 感染频率的影响。
