NK-cell phenotype at interruption underlies widely divergent duration of CD4+-guided antiretroviral treatment interruption
NK-cell phenotype at interruption underlies widely divergent duration of CD4+-guided antiretroviral treatment interruption
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DOI：
10.1093/intimm/dxq462
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发表时间：
2011-02-01
影响因子：
4.4
通讯作者：
De Maria, Andrea
中科院分区：
文献类型：
--
作者：
Bozzano, Federica;Nasi, Milena;De Maria, Andrea
长期副作用可能代表抗逆转录病毒治疗（ART）在HIV感染患者中的相关负担，这些患者在较长时间内具有良好的CD 4免疫重建。已经对CD 4指导的治疗中断（TI）进行了评估，以解决这一问题，并可能导致不同患者队列中的广泛ART停药时间。我们研究了先天免疫反应的差异，特别是NK细胞，是否与较长（LoTI）或较短（ShTI）TI的模式相关。对TI持续时间（18个月）差异很大的一组患者的临床队列参数进行了分析< 9 versus >，包括NK细胞分析和天然细胞毒性受体（NCR）触发的γ-IFN产生的功能。尽管与健康供体相比，在接受ART的LoTI和ShTI患者中观察到NCR表达（NKp 30）和功能持续降低，但在随后发生LoTI过程的患者中，在基线TI时观察到相关差异。NK细胞上NKG 2D和NKp 46的表达较低。因此，在ART期间存在先天免疫平衡的差异，可能与HIV感染的差异控制有关，并且他们的理解可以解释单个患者的临床差异，这些差异不能单独通过CD 4（+）细胞计数来反映。
Long-term side effects may represent a relevant burden of antiretroviral treatment (ART) in HIV-infected patients with good CD4 immune reconstitution over extended time spans. CD4-guided treatment interruption (TI) has been evaluated to address this point and may result in a wide spectrum of time off ART in different patient cohorts. We studied whether differences in innate immune responses, in particular NK cells, are associated to patterns of longer (LoTI) or a shorter (ShTI) TI. Clinical cohort parameters were analyzed on a group of patients widely diverging for TI duration (< 9 versus >18 months) on samples before TI, including NK-cell analysis and function by natural cytotoxicity receptor (NCR)-triggered gamma-IFN production. Although persistently reduced NCR expression (NKp30) and function were observed in both LoTI and ShTI patients on ART compared with healthy donors, relevant differences were observed at baseline TI in those patients who subsequently developed LoTI course. Lower expression of NKG2D and NKp46 on NK cells. This also translates in reduced gamma-IFN production in redirected functional assays.Thus, differences in innate immune balance exist during ART, may be associated to differential control of HIV infection and their understanding could explain clinical differences in individual patients that are not reflected by CD4(+) cell counts alone.