University of Colorado Denver Anschutz Medical Center, Aurora, CO, United States.
University of Witwatersrand, Johannesburg, South Africa.
Front Immunol. 2019 Mar 26;10:595. doi: 10.3389/fimmu.2019.00595. eCollection 2019.
HIV-exposed uninfected infants (HEU) are at higher risk of severe infections, hospitalizations and death compared with HIV-unexposed uninfected infants (HUU), but the immune deficit underlying it is not known. To address this gap, we investigated T cell functionality and its relationship to phenotypic profiles of T cells and antigen presenting cells (APC) in HEU and HUU. Blood mononuclear cells from 55 HEU and 16 HUU were stimulated with Staphylococcal Enterotoxin B (SEB) or mock for 72 h, and tested by flow cytometry for proliferation and expression of Th1, Th2, and regulatory (Treg) markers. In parallel, cells were phenotypically assessed for differentiation profiles of Treg, conventional T cell (Tconv) and APC in unstimulated cells. HEU had lower CD4+ functional responses to SEB/mock and similar CD8+ responses compared with HUU. In the phenotypic T cell panel, HEU showed higher proportions of CD4+ and CD8+ Treg expressing IL10, FOXP3, and CD25; higher effector Tconv and Treg; and lower naïve and CD4+TGFβ+ Treg compared with HUU. In the phenotypic APC panel, HEU showed higher proportions of CD1c+ cDC2, CD123+ pDC, CD16+ inflammatory monocytes and cDC and higher expression of CD103 on CD1c-CD123-CD16-cDC1 compared with HUU. Regression analyses adjusted for HIV exposure and multiple comparisons showed that higher CD8+IL10+ and CD8+FOXP3+ Treg in unstimulated cells were associated with lower CD8+ T cell functional responses to SEB/mock. Functionality was not affected by Tconv differentiation, but higher APC activation in aggregate was associated with higher CD8+IL10+ Treg responses to SEB. T cell functionality was decreased in HEU compared with HUU. High CD8+ Treg proportions were the most important predictors of decreased T cell functionality in HEU and HUU.
HIV 暴露未感染婴儿（HEU）与 HIV 未暴露未感染婴儿（HUU）相比，发生严重感染、住院和死亡的风险更高，但其中的免疫缺陷尚不清楚。为了解决这一差距，我们研究了 HEU 和 HUU 中 T 细胞功能及其与 T 细胞和抗原呈递细胞（APC）表型特征的关系。从 55 名 HEU 和 16 名 HUU 的血液单核细胞中提取，用葡萄球菌肠毒素 B（SEB）或模拟物刺激 72 小时，并用流式细胞术检测增殖和 Th1、Th2 和调节性（Treg）标志物的表达。同时，在未刺激细胞中对 Treg、常规 T 细胞（Tconv）和 APC 的分化谱进行表型评估。HEU 对 SEB/模拟物的 CD4+功能反应较低，而 CD8+反应与 HUU 相似。在表型 T 细胞面板中，HEU 显示出更高比例的表达 IL10、FOXP3 和 CD25 的 CD4+和 CD8+Treg；更高比例的效应 Tconv 和 Treg；以及更低比例的幼稚和 CD4+TGFβ+Treg。在表型 APC 面板中，HEU 显示出更高比例的 CD1c+ cDC2、CD123+ pDC、CD16+炎症单核细胞和 cDC，以及 CD1c-CD123-CD16-cDC1 上更高的 CD103 表达。经 HIV 暴露和多次比较调整的回归分析表明，未刺激细胞中更高比例的 CD8+IL10+和 CD8+FOXP3+Treg 与 SEB/mock 对 CD8+T 细胞功能反应降低相关。功能不受 Tconv 分化的影响，但 APC 的总体激活与 SEB 诱导的 CD8+IL10+Treg 反应升高相关。与 HUU 相比，HEU 中的 T 细胞功能降低。在 HEU 和 HUU 中，高比例的 CD8+Treg 是 T 细胞功能降低的最重要预测因子。
