Prendergast Andrew, O'Callaghan Maria, Menson Esse, Hamadache Djamel, Walters Sam, Klein Nigel, Goulder Philip
Department of Paediatrics, University of Oxford, Oxford, United Kingdom.
AIDS Res Hum Retroviruses. 2012 May;28(5):465-8. doi: 10.1089/AID.2011.0113. Epub 2011 Sep 7.
Immune activation is the best marker of HIV disease progression in both adults and children. However, the factors that drive immune activation in HIV-infected children remain incompletely understood and may differ from those in adults. Immune activation was investigated in a cohort of 93 untreated HIV-infected children, of median age 10.8 years, and 37 HIV-uninfected children. CD8(+) T cell activation, which was higher in HIV-infected than HIV-uninfected children (p<0.001), did not correlate with viral load (R=-0.03, p=0.838). Similarly, programmed death 1 (PD-1) expression on CD8(+) T cells, which was higher in HIV-infected children than HIV-uninfected children (p<0.001), was not associated with viral load (R=0.11, p=0.40), but correlated with CD8 activation (R=0.41, p=0.002). Both CD8 activation and PD-1 expression were partially driven by the magnitude of the HIV-specific CD8(+) T cell response. CD3(+)CD4(+)CD25(hi)FoxP3(+) regulatory T cells (Tregs) were depleted in HIV-infected, compared to HIV-uninfected, children [median 1.0% (IQR 0.6, 1.9) vs. 2.6% (IQR 1.7, 3.2) CD3 cells; p<0.001]. Depletion was associated with increased CD8 activation (R=-0.27, p=0.068), suggesting that the decline in Tregs may allow immune activation to increase. Taken together, immune activation and PD-1 upregulation in children are not directly driven by viral load but may be influenced by the magnitude of the immune response to HIV itself, and to the depletion of Tregs that occurs during HIV infection. Further understanding of the factors that drive immune activation in children is critical to developing future therapeutic strategies in this population.
免疫激活是成人和儿童HIV疾病进展的最佳标志物。然而，驱动HIV感染儿童免疫激活的因素仍未完全明确，可能与成人不同。在一个队列中对93名未接受治疗的HIV感染儿童（中位年龄10.8岁）和37名未感染HIV的儿童进行了免疫激活情况的研究。HIV感染儿童的CD8(+) T细胞激活水平高于未感染HIV的儿童（p<0.001），但与病毒载量无相关性（R=-0.03，p=0.838）。同样，HIV感染儿童CD8(+) T细胞上程序性死亡1（PD-1）的表达高于未感染HIV的儿童（p<0.001），与病毒载量无关（R=0.11，p=0.40），但与CD8激活相关（R=0.41，p=0.002）。CD8激活和PD-1表达均部分由HIV特异性CD8(+) T细胞反应的强度驱动。与未感染HIV的儿童相比，HIV感染儿童的CD3(+)CD4(+)CD25(hi)FoxP3(+)调节性T细胞（Tregs）减少[CD3细胞的中位数分别为1.0%（四分位间距0.6，1.9）和2.6%（四分位间距1.7，3.2）；p<0.001]。Tregs减少与CD8激活增加相关（R=-0.27，p=0.068），这表明Tregs数量的下降可能使免疫激活增加。综上所述，儿童的免疫激活和PD-1上调并非直接由病毒载量驱动，而是可能受对HIV本身的免疫反应强度以及HIV感染期间发生的Tregs减少的影响。进一步了解驱动儿童免疫激活的因素对于制定该人群未来的治疗策略至关重要。
