Robust HIV-specific CD4+ and CD8+ T-cell responses distinguish elite control in adolescents living with HIV from viremic nonprogressors.
Robust HIV-specific CD4+ and CD8+ T-cell responses distinguish elite control in adolescents living with HIV from viremic nonprogressors.
复制标题
DOI：
10.1097/qad.0000000000003078
复制
发表时间：
2022-01-01
期刊：
影响因子：
--
通讯作者：
Goulder P
中科院分区：
文献类型：
--
作者：
Vieira VA;Millar J;Adland E;Muenchhoff M;Roider J;Guash CF;Peluso D;Thomé B;Garcia-Guerrero MC;Puertas MC;Bamford A;Brander C;Carrington M;Martinez-Picado J;Frater J;Tudor-Williams G;Goulder P
精英控制者是未经治疗的艾滋病毒感染者，能够自发控制血浆病毒血症至少一年。尽管病毒血症非进展者在垂直 HIV 感染中比成人感染更常见，但精英控制在儿科人群中很少见。我们通过流式细胞术分析了四名儿科精英控制者 (PEC) 与年龄匹配的非进展者 (PNP)、进展者和 HIV 暴露未感染者 (HEU) 青少年的 T 细胞免疫表型和 HIV 特异性反应。与进展细胞相比，PEC T 细胞群的免疫激活和耗竭水平较低，这反映在更持久和保留的效应功能上。与 PNP 和进展细胞相比，PEC 中的 HIV 特异性 T 细胞反应的特点是高频 Gag 特异性 CD4+ T 细胞活性，以及明显更多的多功能 Gag 特异性 CD8+ 活性。即使在没有 HLA-B*27/57/81 等保护性 HLA-I 分子的情况下，这些发现也得到了一致的观察。儿童精英控制通常是在感染多年后实现的，PNP 中的低免疫激活先于 CD8+ T 细胞反应能力的增强，以在儿童时期实现病毒血症的免疫控制，而在成人中，急性感染中的高免疫激活预示着随后的 CD8+ T 细胞介导的病毒血症免疫控制，而在成人精英控制者中，低免疫激活是急性感染后产生的快速 CD8+ T 细胞介导的免疫控制的结果。 PEC 采用的这种独特策略可能有助于识别促进治疗后控制者缓解的途径，其中保护性 HLA-I 分子不是主要因素。
Elite controllers are therapy-naive individuals living with HIV capable of spontaneous control of plasma viraemia for at least a year. Although viremic nonprogressors are more common in vertical HIV-infection than in adults’ infection, elite control has been rarely characterized in the pediatric population. We analyzed the T-cell immunophenotype and the HIV-specific response by flow cytometry in four pediatric elite controllers (PECs) compared with age-matched nonprogressors (PNPs), progressors and HIV-exposed uninfected (HEUs) adolescents. PECs T-cell populations had lower immune activation and exhaustion levels when compared with progressors, reflected by a more sustained and preserved effector function. The HIV-specific T-cell responses among PECs were characterized by high-frequency Gag-specific CD4+ T-cell activity, and markedly more polyfunctional Gag-specific CD8+ activity, compared with PNPs and progressors. These findings were consistently observed even in the absence of protective HLA-I molecules such as HLA-B∗27/57/81. Pediatric elite control is normally achieved after years of infection, and low immune activation in PNPs precedes the increasing ability of CD8+ T-cell responses to achieve immune control of viraemia over the course of childhood, whereas in adults, high immune activation in acute infection predicts subsequent CD8+ T-cell mediated immune control of viremia, and in adult elite controllers, low immune activation is therefore the consequence of the rapid CD8+ T-cell mediated immune control generated after acute infection. This distinct strategy adopted by PECs may help identify pathways that facilitate remission in posttreatment controllers, in whom protective HLA-I molecules are not the main factor.