Laboratório de AIDS e Imunologia Molecular, Instituto Oswaldo Cruz-IOC, FIOCRUZ, Rio de Janeiro, Brazil.
Instituto Nacional de Infectologia Evandro Chagas-INI, FIOCRUZ, Rio de Janeiro, Brazil.
PLoS One. 2020 Feb 5;15(2):e0228745. doi: 10.1371/journal.pone.0228745. eCollection 2020.
HIV-1 infection is characterized by generalized deregulation of the immune system, resulting in increased chronic immune activation. However, some individuals called HIV controllers (HICs) present spontaneous control of viral replication and have a more preserved immune system. Among HICs, discordant results have been observed regarding immune activation and the frequency of different T cell subsets, including Treg and Th17 cells. We evaluated T cell immune activation, differentiation and regulatory profiles in two groups of HICs-elite controllers (ECs) and viremic controllers (VCs)-and compared them to those of cART-treated individuals (cART) and HIV-1-negative (HIV-neg) individuals. ECs demonstrated similar levels of activated CD4+ and CD8+ T cells in comparison to HIV-neg, while cART and VCs showed elevated T cell activation. CD4+ T cell subset analyses showed differences only for transitional memory T cell frequency between the EC and HIV-neg groups. However, VC individuals showed higher frequencies of terminally differentiated, naïve, and stem cell memory T cells and lower frequencies of transitional memory and central memory T cells compared to the HIV-neg group. Among CD8+ T cell subsets, ECs presented higher frequencies of stem cell memory T cells, while VCs presented higher frequencies of terminally differentiated T cells compared to the HIV-neg group. HICs showed lower frequencies of total Treg cells compared to the HIV-neg and cART groups. ECs also presented higher frequencies of activated and a lower frequency of resting Treg cells than the HIV-neg and cART groups. Furthermore, we observed a high frequency of Th17 cells in ECs and high Th17/Treg ratios in both HIC groups. Our data showed that ECs had low levels of activated T cells and a high frequency of activated Treg and Th17 cells, which could restrict chronic immune activation and be indicative of a preserved mucosal response in these individuals.
HIV-1 感染的特征是免疫系统的广泛失调，导致慢性免疫激活增加。然而，一些被称为 HIV 控制器（HIC）的个体能够自发地控制病毒复制，并拥有更完整的免疫系统。在 HIC 中，关于免疫激活和不同 T 细胞亚群（包括 Treg 和 Th17 细胞）的频率，已经观察到不一致的结果。我们评估了两组 HIC（精英控制器（EC）和病毒血症控制器（VC））的 T 细胞免疫激活、分化和调节特征，并将其与接受 cART 治疗的个体（cART）和 HIV-1 阴性（HIV-neg）个体进行了比较。EC 与 HIV-neg 相比，其激活的 CD4+和 CD8+T 细胞水平相似，而 cART 和 VC 显示出 T 细胞激活的升高。CD4+T 细胞亚群分析仅显示 EC 与 HIV-neg 组之间过渡记忆 T 细胞频率的差异。然而，VC 个体表现出更高频率的终末分化、幼稚和干细胞记忆 T 细胞，以及更低频率的过渡记忆和中央记忆 T 细胞，与 HIV-neg 组相比。在 CD8+T 细胞亚群中，EC 表现出更高频率的干细胞记忆 T 细胞，而 VC 表现出比 HIV-neg 组更高频率的终末分化 T 细胞。与 HIV-neg 和 cART 组相比，HIC 显示出更低频率的总 Treg 细胞。EC 也表现出更高频率的激活 Treg 细胞和更低频率的静息 Treg 细胞，与 HIV-neg 和 cART 组相比。此外，我们观察到 EC 中 Th17 细胞的高频率和两个 HIC 组中 Th17/Treg 比值较高。我们的数据表明，EC 具有低水平的激活 T 细胞和高频率的激活 Treg 和 Th17 细胞，这可能限制慢性免疫激活，并表明这些个体中存在完整的粘膜反应。
