Yang Hongbing, Wu Hao, Hancock Gemma, Clutton Genevieve, Sande Nellia, Xu Xiaoning, Yan Huiping, Huang Xiaojie, Angus Brian, Kuldanek Kristin, Fidler Sarah, Denny Thomas N, Birks Jacqueline, McMichael Andrew, Dorrell Lucy
Oxford NIHR Biomedical Research Centre, United Kingdom.
J Infect Dis. 2012 Aug 15;206(4):552-61. doi: 10.1093/infdis/jis379. Epub 2012 Jun 18.
Rare human immunodeficiency virus type 1 (HIV-1)-infected individuals who maintain control of viremia without therapy show potent CD8+ T-cell-mediated suppression of viral replication in vitro. Whether this is a determinant of the rate of disease progression in viremic individuals is unknown.
We measured CD8+ T-cell-mediated inhibition of a heterologous HIV-1 isolate in 50 HIV-1-seropositive adults with diverse progression rates. Linear mixed models were used to determine whether CD8+ T-cell function could explain variation in the rate of CD4+ T-cell decline.
There was a significant interaction between CD8+ T-cell antiviral activity in vitro and the rate of CD4+ T-cell decline in chronically infected individuals (P < .0001). In a second prospective analysis of recently infected subjects followed for up to 3 years, CD8+ T-cell antiviral activity strongly predicted subsequent CD4+ T-cell decline (P < .0001) and explained up to 73% of the interindividual variation in the CD4+ T-cell slope. In addition, it was inversely associated with viral load set point (r = -0.68 and P = .002).
The antiviral inhibitory capacity of CD8+ T cells is highly predictive of CD4+ T-cell loss in early HIV-1 infection. It has potential as a benchmark of effective immunity in vaccine evaluation.
在未接受治疗的情况下维持病毒血症控制的罕见人类免疫缺陷病毒1型（HIV-1）感染个体，在体外显示出有效的CD8 + T细胞介导的病毒复制抑制作用。这是否是病毒血症个体疾病进展速度的决定因素尚不清楚。
我们在50名具有不同进展速度的HIV-1血清阳性成人中测量了CD8 + T细胞介导的对异源HIV-1分离株的抑制作用。使用线性混合模型来确定CD8 + T细胞功能是否可以解释CD4 + T细胞下降速率的变化。
在慢性感染个体中，体外CD8 + T细胞抗病毒活性与CD4 + T细胞下降速率之间存在显著相互作用（P <.0001）。在对最近感染的受试者进行长达3年的第二次前瞻性分析中，CD8 + T细胞抗病毒活性强烈预测了随后的CD4 + T细胞下降（P <.0001），并解释了CD4 + T细胞斜率个体间差异的73%。此外，它与病毒载量设定点呈负相关（r = -0.68，P =.002）。
CD8 + T细胞的抗病毒抑制能力高度预测早期HIV-1感染中CD4 + T细胞的损失。它有潜力作为疫苗评估中有效免疫的基准。
