Terminal Differentiation of CD56dim CD16+ Natural Killer Cells Is Associated with Increase in Natural Killer Cell Frequencies After Antiretroviral Treatment in HIV-1 Infection
Terminal Differentiation of CD56dim CD16+ Natural Killer Cells Is Associated with Increase in Natural Killer Cell Frequencies After Antiretroviral Treatment in HIV-1 Infection
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DOI：
10.1089/aid.2015.0115
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发表时间：
2015-12-01
影响因子：
1.5
通讯作者：
Schmidt, Reinhold E.
中科院分区：
文献类型：
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作者：
Ahmad, Fareed;Tufa, Dejene Milkessa;Schmidt, Reinhold E.
HIV-1感染导致自然杀伤(NK)细胞免疫异常，如NK细胞亚群分布紊乱，抑制性受体激活和上调下调，从而降低NK细胞的杀伤能力和细胞因子的分泌。抗逆转录病毒治疗(ART)可以恢复NK细胞的表型和功能。然而，ART对NK细胞终末分化、激活和紊乱分布的影响尚未得到纵向研究。在这里，我们在纵向和横向研究中分析了ART对外周血NK细胞这些参数的影响。我们观察到初治HIV-1患者扩增的CD56(-)CD16(+)NK细胞频率与CD56(Dim)CD16(+)NK细胞频率呈负相关。ART后CD56(Dim)CD16(+)丢失，CD56(-)CD16(+)NK细胞扩增恢复至正常对照组水平。抗逆转录病毒治疗后不同NK细胞亚群增强的免疫活性部分恢复。CD57表达检测显示，ART后CD56(Dim)CD16(+)NK细胞的终末分化增强。CD57(+)CD56(DIM)CD16(+)NK细胞频率与总NK细胞频率呈正相关，提示ART后CD57(+)CD56(DIM)CD16(+)NK细胞频率的增加反映为总NK细胞频率的增加。综上所述，ART对NK细胞的免疫修复有一定的作用，并能促进CD56(Dim)CD16(+)NK细胞的终末分化，这与ART后NK细胞总数的增加有关。
HIV-1 infection results in immunological abnormalities of natural killer (NK) cells such as disturbed distribution of NK cell subsets and downmodulation of activating and upregulation of inhibitory receptors thereby diminishing NK cell killing capacity and cytokine secretion. Antiretroviral treatment (ART) is known to restore phenotype and functions of NK cells. However, the effects of ART on NK cell terminal differentiation, activation, and disturbed distribution have not been studied yet longitudinally. Here, we analyzed the effects of ART on these parameters of peripheral blood NK cells in a longitudinal as well as in a cross-sectional study. We observed that expanded CD56(-)CD16(+) NK cell frequency is inversely correlated with the frequency of CD56(dim)CD16(+) NK cells in treatment-naive HIV-1 patients. Loss of CD56(dim)CD16(+) and expansion of CD56(-)CD16(+) NK cells again restore to the levels of healthy controls after ART. Enhanced immune activation of different NK cell subsets is partially restored after ART. Terminal differentiation of CD56(dim)CD16(+) NK cells is enhanced after ART as measured by CD57 expression. Frequencies of CD57(+)CD56(dim)CD16(+) NK cells are directly correlated with the frequencies of total NK cells suggesting that an increase in the frequencies of CD57(+)CD56(dim)CD16(+) NK cells is reflected by increased frequencies of total NK cells after ART. Taken together these data demonstrate that ART has an effect on the immune restoration of NK cells and is enhanced in the terminal differentiation of CD56(dim)CD16(+) NK cells, which is associated with increased frequencies of total NK cells after ART.