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在接受抗逆转录病毒治疗的HIV患者中,自然杀伤细胞能否弥补CD4 + T细胞对巨细胞病毒反应的受损?

Could natural killer cells compensate for impaired CD4+ T-cell responses to CMV in HIV patients responding to antiretroviral therapy?

作者信息

Tan Dino Bee Aik, Fernandez Sonia, French Martyn, Price Patricia

机构信息

School of Pathology and Laboratory Medicine, University of Western Australia, Australia.

出版信息

Clin Immunol. 2009 Jul;132(1):63-70. doi: 10.1016/j.clim.2009.03.518. Epub 2009 Apr 28.

Abstract

We evaluated NK cell subsets and functions in previously immunodeficient HIV patients responding to ART. Cytokine receptor mRNA was quantitated in purified CD56+ cells. Data were correlated with CD4+ T-cell counts and IFNgamma responses to CMV. NK cell IFNgamma responses to K562 cells and proportions of CD56lo NK cells were correlated in patients (p < 0.001) and both were lower than in controls (p < 0.001 and p = 0.008, respectively), so all patients had poor NK cell function. Proportions of CD56hi NK cells correlated inversely with current CD4+ T-cell counts (p = 0.006) and perforin expression in CD56hi NK cells was higher in patients than controls (p < 0.05). Hence increased proportions and cytolytic function of CD56hi NK cells may partially compensate for CD4+ T-cell deficiency. NK cell IFNgamma responses correlated inversely with expression of IL-10 and IL-12 receptor mRNA. Expression of these transcripts is reduced by exposure to the cytokines, which may reflect immune activation in immunodeficient patients.

摘要

我们评估了既往免疫缺陷的HIV患者在接受抗逆转录病毒治疗(ART)时的自然杀伤(NK)细胞亚群及功能。对纯化的CD56⁺细胞中的细胞因子受体信使核糖核酸(mRNA)进行定量分析。数据与CD4⁺T细胞计数以及对巨细胞病毒(CMV)的γ干扰素(IFNγ)反应相关。患者的NK细胞对K562细胞的IFNγ反应与CD56低表达NK细胞比例相关(p<0.001),且两者均低于对照组(分别为p<0.001和p = 0.008),因此所有患者的NK细胞功能均较差。CD56高表达NK细胞比例与当前CD4⁺T细胞计数呈负相关(p = 0.006),且患者CD56高表达NK细胞中的穿孔素表达高于对照组(p<0.05)。因此,CD56高表达NK细胞比例增加及其细胞溶解功能可能部分补偿CD4⁺T细胞缺陷。NK细胞IFNγ反应与白细胞介素10(IL-10)和IL-12受体mRNA的表达呈负相关。暴露于这些细胞因子会使这些转录本的表达降低,这可能反映了免疫缺陷患者的免疫激活情况。

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