Myeloid-Derived Suppressor Cells Regulate Immune Response in Patients with Chronic Hepatitis B Virus Infection through PD-1-Induced IL-10
Myeloid-Derived Suppressor Cells Regulate Immune Response in Patients with Chronic Hepatitis B Virus Infection through PD-1-Induced IL-10
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DOI：
10.4049/jimmunol.1400849
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发表时间：
2014-12-01
影响因子：
4.4
通讯作者：
Guo, YaJun
中科院分区：
文献类型：
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作者：
Huang, Ang;Zhang, Bo;Guo, YaJun
尽管髓系来源的抑制细胞(MDSCs)在多种病理条件下具有免疫抑制功能，但MDSCs在乙肝病毒感染中的作用尚不清楚。本研究对91例慢性乙型病毒性肝炎(CHB)患者外周血和肝脏中MDSCs的频率和功能进行了研究。CHB患者外周血中CD14(+)、HLADR-/LOW的MDSCs比例明显高于健康对照组。此外，还检测到该人群中程序性死亡1(PD-1)的高表达和IL-10的分泌。MDSCs频率与血清病毒载量呈正相关，与肝脏炎性损伤呈负相关。这些细胞在慢性乙肝患者的肝组织中也很丰富，并与坏死性炎症活动有关。此外，我们发现这些细胞可以抑制乙肝病毒特异性CD8(+)T细胞的反应，包括减少增殖和干扰素-γ的产生，并抑制CD8(+)T细胞的脱颗粒，包括减少颗粒酶B和穿孔素的产生。重要的是，PD-1诱导MDSCs产生IL-10是其抑制活性的机制之一。据我们所知，我们的研究首次证明，CHB患者中的CD14(+)HLA-DR-/lowPD-1(+)MDSCs有助于对病毒的免疫应答不足，并导致慢性感染，这是治疗干预的潜在靶点。
Although myeloid-derived suppressor cells (MDSCs) are well known for their immunosuppressive function in several pathological conditions, the role of MDSCs in hepatitis B virus infection remains obscure. In this study, we investigated the frequency and function of MDSCs in the peripheral blood and liver of 91 chronic hepatitis B (CHB) patients. A higher percentage ofMDSCs, defined as CD14(+) HLA-DR-/low, was detected in peripheral blood of CHB patients than that of the healthy controls. Moreover, high expression of programmed death 1 (PD-1) and secretion of IL-10 in this population were determined. The frequency of MDSCs was positively correlated with serum viral load, but it was negatively correlated with liver inflammatory injury. These cells were also abundant in liver tissue of CHB patients and were related to necroinflammatory activity. Furthermore, we found that these cells could suppress hepatitis B virus-specific CD8(+) T cell response, including reduced proliferation and IFN-gamma production, and inhibit degranulation of CD8(+) T cells, including reduced production of granzyme B and perforin. Importantly, PD-1-induced IL-10 production by MDSCs was responsible for the suppressive activity. To our knowledge, for the first time our study proved that CD14(+)HLA-DR-/lowPD-1(+) MDSCs in CHB patients contribute to an inadequate immune response against the virus and lead to chronic infection, which represents a potential target for therapeutic intervention.