Sáez-Cirión Asier, Sinet Martine, Shin So Youn, Urrutia Alejandra, Versmisse Pierre, Lacabaratz Christine, Boufassa Faroudy, Avettand-Fènoël Véronique, Rouzioux Christine, Delfraissy Jean-François, Barré-Sinoussi Françoise, Lambotte Olivier, Venet Alain, Pancino Gianfranco
Institut Pasteur, Unité de Régulation des Infections Rétrovirales, Paris, France.
J Immunol. 2009 Jun 15;182(12):7828-37. doi: 10.4049/jimmunol.0803928.
"HIV controllers" (HICs) are rare individuals in whom HIV-1 plasma viral load remains undetectable without antiretroviral treatment. This spontaneous viral control in HICs is usually associated to strong functional HIV-specific CD8(+) T cell responses. Accordingly, we have recently shown that CD8(+) T cells from HICs strongly suppress ex vivo HIV-1 infection of autologous CD4(+) T cells, suggesting a crucial role of this response in vivo. Knowledge of the mechanisms underlying the CD8(+) T cell antiviral activity might help to develop effective T cell-based vaccines. In the present work, we further characterized the HIV-suppressive capacity of CD8(+) T cells in 19 HICs. CD8(+) T cells from 14 of the 19 HICs showed strong HIV-suppressive capacity ex vivo. This capacity was stable over time and was partially effective even on other primate lentiviruses. HIV-suppressive capacity of CD8(+) T cells correlated strongly with the frequency of HIV-specific CD8(+) T cells, and in particular of Gag-specific CD8(+) T cells. We also identified five HICs who had weak HIV-suppressive CD8(+) T cell capacities and HIV-specific CD8(+) T cell responses. Among these five HICs, at least three had highly in vitro replicative viruses, suggesting that the control of viremia in these patients is not due to replication-defective viruses. These results, on the one hand, suggest the importance of Gag responses in the antiviral potency of CD8(+) T cells from HICs and, on the other hand, propose that other host mechanisms may contribute to restraining HIV infection in HICs.
“HIV 控制者”（HICs）是一类罕见个体，即便未接受抗逆转录病毒治疗，其 HIV-1 血浆病毒载量仍无法检测到。HICs 这种自发的病毒控制通常与强大的功能性 HIV 特异性 CD8(+) T 细胞反应相关。相应地，我们最近发现，HICs 的 CD8(+) T 细胞能在体外强烈抑制自体 CD4(+) T 细胞的 HIV-1 感染，这表明该反应在体内发挥着关键作用。了解 CD8(+) T 细胞抗病毒活性的潜在机制可能有助于研发有效的基于 T 细胞的疫苗。在本研究中，我们进一步对 19 名 HICs 的 CD8(+) T 细胞的 HIV 抑制能力进行了表征。19 名 HICs 中有 14 名的 CD8(+) T 细胞在体外表现出强大的 HIV 抑制能力。这种能力随时间稳定，甚至对其他灵长类慢病毒也有部分抑制效果。CD8(+) T 细胞的 HIV 抑制能力与 HIV 特异性 CD8(+) T 细胞，特别是 Gag 特异性 CD8(+) T 细胞的频率密切相关。我们还鉴定出 5 名 HICs，他们的 CD8(+) T 细胞的 HIV 抑制能力较弱，HIV 特异性 CD8(+) T 细胞反应也较弱。在这 5 名 HICs 中，至少有 3 名携带高度可在体外复制的病毒，这表明这些患者病毒血症的控制并非源于复制缺陷型病毒。这些结果一方面表明 Gag 反应在 HICs 的 CD8(+) T 细胞抗病毒效力中的重要性，另一方面表明其他宿主机制可能有助于抑制 HICs 中的 HIV 感染。
