在接受治疗但CD4+ T细胞恢复不佳的HIV感染患者的CD4+ T细胞中，对白细胞介素-7（IL-7）而非干扰素-α（IFN-α）的反应性降低。
Responsiveness to IL-7 but not to IFN-α is diminished in CD4+ T cells from treated HIV infected patients who experience poor CD4+ T-cell recovery.
作者信息
Nguyen Thao P, Shukla Supriya, Asaad Robert, Freeman Michael L, Lederman Michael M, Harding Clifford V, Sieg Scott F
机构信息
aDepartment of Medicine, Division of Infectious Diseases and HIV Medicine bDepartment of Pathology, Case Western Reserve University/University Hospitals Case Medical Center cCenter for AIDS Research, Case Western Reserve University, Cleveland, Ohio, USA.
出版信息
AIDS. 2016 Aug 24;30(13):2033-42. doi: 10.1097/QAD.0000000000001161.
OBJECTIVE
To assess CD4 T-cell responsiveness to IL-7 and IFN-α in HIV-infected patients who experience poor recovery of CD4 T-cell counts during therapy (immune failure patients).
DESIGN
Responses to IL-7 and IFN-α were compared between HIV-infected immune failure (CD4 cell counts <379 cells/μl) patients and immune success (CD4 cell counts >500 cells/μl) as well as healthy control patients.
METHODS
Flow cytometry was used to assess peripheral blood mononuclear cells for IL-7-induced proliferation, CD25 expression, and signaling (signal transducer and activator of transcription 5 phosphorylation and Akt phosphorylation) in CD4 T cells. Freshly isolated cells were characterized by expression of IL-7Rα (CD127) among CD4 T-cell maturation subsets by flow cytometry and sorted CD3 T cells were assessed for expression of IFN-α and interferon stimulated genes (2'-5'-oligoadenylate synthetase-1 and myxovirus resistance A protein) by quantitative real-time PCR. Responses to IFN-α were assessed by induction of signal transducer and activator of transcription 1 phosphorylation and inhibition of IL-7-induced CD4 T-cell proliferation.
RESULTS
IL-7-induced proliferation and CD25 expression were decreased in CD4 T cells from immune failure patients. CD127 expressing CD4 T cells were decreased, whereas expression of 2'-5'-oligoadenylate synthetase-1, myxovirus resistance A protein, and IFN-α mRNA were increased in total CD3 T cells from immune failure patients. CD127 expression correlated with CD25 induction but not proliferation, whereas T-cell IFN-α mRNA was associated with reduced proliferation in CD4 T cells from immune failure patients. IFN-α-mediated induction of signal transducer and activator of transcription 1 phosphorylation and inhibition of proliferation were not diminished in CD4 T cells from immune failure patients.
CONCLUSION
IL-7 responsiveness is impaired in immune failure patients and may be related to expression of CD127 and IFN-α.
目的
评估在治疗期间CD4 T细胞计数恢复不佳的HIV感染患者（免疫衰竭患者）中，CD4 T细胞对白细胞介素-7（IL-7）和干扰素-α（IFN-α）的反应性。
设计
比较HIV感染的免疫衰竭患者（CD4细胞计数<379个/μl）、免疫成功患者（CD4细胞计数>500个/μl）以及健康对照患者对IL-7和IFN-α的反应。
方法
采用流式细胞术评估外周血单个核细胞中IL-7诱导的增殖、CD25表达以及CD4 T细胞中的信号传导（信号转导和转录激活因子5磷酸化和Akt磷酸化）。通过流式细胞术对新鲜分离的细胞按CD4 T细胞成熟亚群中的IL-7Rα（CD127）表达进行表征，并通过定量实时聚合酶链反应评估分选的CD3 T细胞中IFN-α和干扰素刺激基因（2'-5'-寡腺苷酸合成酶-1和抗黏液病毒A蛋白）的表达。通过诱导信号转导和转录激活因子1磷酸化以及抑制IL-7诱导的CD4 T细胞增殖来评估对IFN-α的反应。
结果
免疫衰竭患者的CD4 T细胞中，IL-7诱导的增殖和CD25表达降低。免疫衰竭患者的总CD3 T细胞中，表达CD127的CD4 T细胞减少，而2'-5'-寡腺苷酸合成酶-1、抗黏液病毒A蛋白和IFN-α mRNA的表达增加。CD127表达与CD25诱导相关，但与增殖无关，而免疫衰竭患者的CD4 T细胞中，T细胞IFN-α mRNA与增殖减少相关。免疫衰竭患者的CD4 T细胞中，IFN-α介导的信号转导和转录激活因子1磷酸化诱导以及增殖抑制并未减弱。
结论
免疫衰竭患者的IL-7反应性受损，可能与CD127和IFN-α的表达有关。
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