Oxford NIHR Biomedical Research Centre, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Eur J Immunol. 2013 Nov;43(11):2875-85. doi: 10.1002/eji.201343646. Epub 2013 Aug 29.
Interleukin-10 (IL-10) plays a key role in regulating proinflammatory immune responses to infection but can interfere with pathogen clearance. Although IL-10 is upregulated throughout HIV-1 infection in multiple cell subsets, whether this is a viral immune evasion strategy or an appropriate response to immune activation is unresolved. Analysis of IL-10 production at the single cell level in 51 chronically infected subjects (31 antiretroviral (ART) naïve and 20 ART treated) showed that a subset of CD8(+) T cells with a CD25(neg) FoxP3(neg) phenotype contributes substantially to IL-10 production in response to HIV-1 gag stimulation. The frequencies of gag-specific IL-10- and IFN-γ-producing T cells in ART-naïve subjects were strongly correlated and the majority of these IL-10(+) CD8(+) T cells co-produced IFN-γ; however, patients with a predominant IL-10(+) /IFN-γ(neg) profile showed better control of viraemia. Depletion of HIV-specific CD8(+) IL-10(+) cells from PBMCs led to upregulation of CD38 on CD14(+) monocytes together with increased IL-6 production, in response to gag stimulation. Increased CD38 expression was positively correlated with the frequency of the IL-10(+) population and was also induced by exposure of monocytes to HIV-1 in vitro. Production of IL-10 by HIV-specific CD8(+) T cells may represent an adaptive regulatory response to monocyte activation during chronic infection.
白细胞介素-10（IL-10）在调节感染时的促炎免疫反应中起着关键作用，但它也可能干扰病原体的清除。尽管在 HIV-1 感染的多个细胞亚群中，IL-10 被上调，但这是一种病毒免疫逃避策略还是对免疫激活的适当反应仍未解决。对 51 名慢性感染患者（31 名未接受抗逆转录病毒（ART）治疗和 20 名接受 ART 治疗）的单个细胞水平的 IL-10 产生进行分析，结果表明，CD25（neg）FoxP3（neg）表型的 CD8（+）T 细胞亚群对 HIV-1 gag 刺激的 IL-10 产生有很大贡献。在未接受 ART 治疗的患者中，gag 特异性 IL-10 和 IFN-γ产生 T 细胞的频率呈强相关性，并且这些 IL-10（+）CD8（+）T 细胞大多数共同产生 IFN-γ；然而，具有主要 IL-10（+）/IFN-γ（neg）特征的患者对病毒血症的控制更好。从 PBMC 中耗尽 HIV 特异性 CD8（+）IL-10（+）细胞会导致 CD14（+）单核细胞上 CD38 的上调，同时增加 IL-6 的产生，这是对 gag 刺激的反应。CD38 表达的增加与 IL-10（+）群体的频率呈正相关，并且还可以通过体外暴露于 HIV-1 来诱导单核细胞的 CD38 表达。HIV 特异性 CD8（+）T 细胞产生的 IL-10 可能代表在慢性感染期间对单核细胞激活的适应性调节反应。
