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.
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.
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DOI：
10.1097/qad.0000000000001161
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发表时间：
2016-08-24
期刊：
影响因子：
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通讯作者：
Sieg SF
中科院分区：
文献类型：
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作者：
Nguyen TP;Shukla S;Asaad R;Freeman ML;Lederman MM;Harding CV;Sieg SF
评估治疗期间CD 4 T细胞计数恢复不良的HIV感染患者（免疫失败受试者）的CD 4 + T细胞对IL-7和IFN-α的反应性。在HIV感染的免疫失败（CD 4计数< 379）受试者和免疫成功（CD 4计数>500）受试者以及健康对照受试者之间比较对IL-7和IFN-α的应答。流式细胞术用于评估外周血单核细胞的IL-7诱导的增殖、CD 4 + T细胞中的CD 25表达和信号传导（P-STAT 5和P-Akt）。通过流式细胞术表征新鲜分离的细胞在CD 4 + T细胞成熟亚群中的IL-7 R α（CD 127）表达，并通过qRT-PCR评估分选的CD 3 + T细胞的IFN-α和干扰素刺激基因（OAS 1和MxA）表达。通过诱导P-STAT 1和抑制IL-7诱导的CD 4 + T细胞增殖来评估对IFN-α的应答。IL-7诱导的增殖和CD 25表达在免疫失败受试者的CD 4 + T细胞中降低。免疫失败受试者的总CD 3 + T细胞中表达CD 127的CD 4 + T细胞减少，而OAS 1、MxA和IFN-α mRNA的表达增加。CD 127表达与CD 25诱导相关，但与增殖无关，而T细胞IFN-α mRNA与免疫失败受试者的CD 4 + T细胞增殖减少相关。在免疫失败受试者的CD 4 + T细胞中，IFN-α介导的P-STAT 1诱导和增殖抑制并未减弱。IL-7反应性在免疫失败受试者中受损，并且可能与CD 127和IFN-α的表达有关。
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 subjects). Responses to IL-7 and IFN-α were compared between HIV infected immune failure (CD4 counts < 379) subjects and immune success (CD4 counts >500) as well as healthy control subjects. Flow cytometry was used to assess peripheral blood mononuclear cells for IL-7 induced proliferation, CD25 expression and signaling (P-STAT5 and P-Akt) 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 (OAS1 and MxA) by qRT-PCR. Responses to IFN-α were assessed by induction of P-STAT1 and inhibition of IL-7-induced CD4+ T cell proliferation. IL-7-induced proliferation and CD25 expression were decreased in CD4+ T cells from immune failure subjects. CD127 expressing CD4+ T cells were decreased while expression of OAS1, MxA and IFN-α mRNA were increased in total CD3+ T cells from immune failure subjects. 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 subjects. IFN-α mediated induction of P-STAT1 and inhibition of proliferation were not diminished in CD4+ T cells from immune failure subjects. IL-7 responsiveness is impaired in immune failure subjects and may be related to expression of CD127 and IFN-α.