CD56+T cells inhibit HIV-1 infection of macrophages

CD56+T cells inhibit HIV-1 infection of macrophages
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DOI:
10.1189/jlb.0312146
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发表时间:
2012-08-01
影响因子:
5.5
通讯作者:
Ho, Wen-Zhe
Ho, Wen-Zhe
中科院分区:
医学3区
文献类型:
--
作者:
Hou, Wei;Ye, Li;Ho, Wen-Zhe

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CD 56 + T细胞是宿主先天免疫系统的重要组成部分,在防御病毒感染中发挥重要作用。我们研究了原代CD 56 + T细胞的非细胞溶解性抗HIV-1活性。从CD 56 + T细胞培养物收集的SN抑制HIV-1感染和复制。这种CD 56 + T SN介导的抗HIV- 1活性是广谱的,因为CD 56 + T SN可以抑制实验室适应的HIV-1和临床株的感染。IFN-γ抗体可部分阻断CD 56 + T SN介导的抗HIV作用。对CD 56 + T细胞作用于HIV-1的机制的研究表明,尽管CD 56 + T SN对HIV-1进入辅助受体CCR 5的表达几乎没有影响,但CD 56 + T SN诱导CCR 5的配体CC-趋化因子的表达。CC趋化因子的抗体也显著阻断了CD 56 + T SN介导的抗HIV活性。此外,CD 56 + T SN还可上调STAT-1/-2的表达,增强IRF 1、IRF 3、IRF 7和IRF 9的表达,从而诱导巨噬细胞内源性IFN-α/β的表达。此外,CD 56 + T SN上调细胞内APOBEC 3G/3F的表达,APOBEC 3G/3F是最近鉴定的HIV-1限制性因子。这些发现提供了令人信服的证据,表明CD 56 + T细胞可能在对抗HIV-1感染的先天免疫中发挥关键作用。J.利瓦克92:343-351; 2012.
CD56+ T cells, the crucial component of the host innate immune system, play an important role in defense against viral infections. We investigated the noncytolytic anti-HIV-1 activity of primary CD56+ T cells. SNs collected from CD56+ T cell cultures inhibited HIV-1 infection and replication. This CD56+ T SN-mediated anti-HIV- 1 activity was broad-spectrum, as CD56+ T SNs could inhibit infections by laboratory-adapted and clinical strains of HIV-1. The antibody to IFN-gamma could partially block the CD56+ T SN-mediated anti-HIV effect. Investigation of mechanism(s) of the CD56+ T cell action on HIV-1 showed that although CD56+ T SN had little effect on HIV-1 entry coreceptor CCR5 expression, CD56+ T SN induced the expression of CC-chemokines, the ligands for CCR5. The antibodies to CCchemokines also significantly blocked CD56+ T SN-mediated anti-HIV activity. Furthermore, CD56+ T SN upregulated the expression of STAT-1/-2 and enhanced the expression of IRF1, -3, -7, and -9, resulting in the induction of endogenous IFN-alpha/beta expression in macrophages. Moreover, CD56+ T SN up-regulated intracellular expression of APOBEC3G/3F, the recently identified HIV-1 restriction factors. These findings provide compelling evidence that CD56+ T cells may have a critical role in innate immunity against HIV-1 infection. J. Leukoc. Biol. 92: 343-351; 2012.