Antiviral Inhibitory Capacity of CD8+ T cells Predicts the Rate of CD4+ T-Cell Decline in HIV-1 Infection
Antiviral Inhibitory Capacity of CD8+ T cells Predicts the Rate of CD4+ T-Cell Decline in HIV-1 Infection
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DOI：
10.1093/infdis/jis379
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发表时间：
2012-08-15
影响因子：
6.4
通讯作者：
Dorrell, Lucy
中科院分区：
文献类型：
--
作者：
Yang, Hongbing;Wu, Hao;Dorrell, Lucy
背景罕见的人类免疫缺陷病毒1型（HIV-1）感染者在没有治疗的情况下保持病毒血症的控制，在体外显示出有效的CD 8 + T细胞介导的病毒复制抑制。这是否是病毒血症个体疾病进展速率的决定因素尚不清楚。我们测量了CD 8 + T细胞介导的抑制异源HIV-1分离在50 HIV-1血清阳性成人不同的进展率。线性混合模型用于确定CD 8 + T细胞功能是否可以解释CD 4 + T细胞下降率的变化。在慢性感染个体中，体外CD 8 + T细胞抗病毒活性与CD 4 + T细胞下降率之间存在显著的相互作用（P <0.0001）。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，CD 8 + T细胞抗病毒活性强烈预测了随后的CD 4 + T细胞下降（P < .0001），并解释了CD 4 + T细胞斜率中高达73%的个体间变异。此外，它与病毒载量设定点呈负相关（r = -0.68，P = 0.002）。CD 8 + T细胞的抗病毒抑制能力是HIV-1感染早期CD 4 + T细胞丢失的高度预测因素。它有潜力作为疫苗评价中有效免疫的基准。
Background. 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.Methods. 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.Results. 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).Conclusions. 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.