Laboratory of Immunovirology, Institute of Biomedicine of Seville, IBiS, Virgen del Rocío University Hospital/CSIC/University of Seville, Seville 41013, Spain.
Laboratory of Immunovirology, Institute of Biomedicine of Seville, IBiS, Virgen del Rocío University Hospital/CSIC/University of Seville, Seville 41013, Spain.
J Infect. 2018 Jan;76(1):86-92. doi: 10.1016/j.jinf.2017.10.010. Epub 2017 Oct 25.
Despite the fact that antiretroviral therapy (cART) suppresses HIV-viremia, an adequate CD4 T-cell recovery is not always achieved (immunodiscordant response to cART). IL17a-producing CD4 T-cells (Th17) constitutes an important subset involved in the preservation of mucosal surfaces integrity, which depletion has been associated with disease progression in HIV-infection. However, whether Th17 frequency at cART initiation is associated with a poor CD4 T-cell recovery has not been yet explored. Our aim was to explore whether the Th17 cells and other IL17a-producing T-cell subsets at cART initiation were associated with a subsequent immunodiscordant response to cART.
We selected pre-cART samples of antiretroviral-naïve subjects with and without a low CD4 recovery after cART (LR-subjects and HR-subjects, respectively). Peripheral blood mononuclear cells (PBMCs) were stimulated with PMA/ionomycine, and the production of several cytokines including IL17a was analyzed by flow cytometry.
A trend to higher Th17 (p = 0.05) and increased frequencies of IL17a-producing Treg (p = 0.011) was found in LR-subjects before cART onset. Despite increased frequencies of both Treg and Th17 in LR-subject at cART initiation, no alteration of Treg/Th17 ratio was observed. While polifunctional profile of CD4 T-cells was not different, frequencies of CD4 T-cells producing cytokine-combinations including IL17a were increased in LR-subjects.
Increased frequencies of Th17, IL17a-producing Treg and CD4 T-cells producing specific IL17a-containing combinations of cytokines, precede the immunodiscordant response to cART, suggesting a potential contribution of these subsets in such anomalous response to cART.
尽管抗逆转录病毒疗法（cART）能抑制 HIV 病毒血症，但并非总能实现充分的 CD4 T 细胞恢复（对 cART 的免疫不和谐反应）。产生白细胞介素 17a（IL17a）的 CD4 T 细胞（Th17）是参与维持黏膜表面完整性的重要亚群，其耗竭与 HIV 感染的疾病进展有关。然而，cART 起始时 Th17 细胞频率是否与 CD4 T 细胞恢复不良相关尚未得到探索。我们的目的是探讨 cART 起始时 Th17 细胞和其他产生 IL17a 的 T 细胞亚群与随后对 cART 的免疫不和谐反应是否相关。
我们选择了 cART 后 CD4 恢复不良（LR 受试者）和恢复良好（HR 受试者）的抗逆转录病毒初治受试者的 cART 前样本。用 PMA/离子霉素刺激外周血单核细胞（PBMCs），并用流式细胞术分析包括 IL17a 在内的几种细胞因子的产生。
在 cART 开始前，LR 受试者中 Th17（p=0.05）和产生 IL17a 的 Treg（p=0.011）的频率有升高的趋势。尽管 LR 受试者在 cART 开始时 Treg 和 Th17 的频率增加，但 Treg/Th17 比值没有改变。虽然 CD4 T 细胞的多功能谱没有差异，但在 LR 受试者中，产生包括 IL17a 在内的细胞因子组合的 CD4 T 细胞的频率增加。
Th17、产生 IL17a 的 Treg 和产生特定含有 IL17a 的细胞因子组合的 CD4 T 细胞的频率增加，先于对 cART 的免疫不和谐反应，表明这些亚群可能对这种异常的 cART 反应有贡献。
