Regulatory NK cells mediated between immunosuppressive monocytes and dysfunctional T cells in chronic HBV infection.
Regulatory NK cells mediated between immunosuppressive monocytes and dysfunctional T cells in chronic HBV infection.
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慢性 HBV 感染中免疫抑制单核细胞和功能失调的 T 细胞之间介导的调节性 NK 细胞
作者：
Li H;Zhai N;Wang Z;Song H;Yang Y;Cui A;Li T;Wang G;Niu J;Crispe IN;Su L;Tu Z
背景和目的HBV感染是世界范围内的一个主要健康问题，但HBV引起慢性持续性感染的免疫学机制仅部分了解。最近，在单核细胞和自然杀伤细胞（NK）中发现了具有抑制特征的细胞亚群。在这里，我们研究了HBV对单核细胞和NK细胞的影响。方法采用流式细胞术、实时荧光定量pcr （qRT -PCR）、酶联免疫吸附试验（ELISA）和免疫印迹法（western blotting）对慢性hbv感染者和健康对照的单核细胞和NK细胞进行表型、基因表达和细胞因子分泌的检测。单核细胞和NK细胞的培养和共培养采用细胞内细胞因子染色法测定NK细胞的活化情况。结果慢性HBV感染患者单核细胞PD-L1、HLA-E、白细胞介素(IL)-10和TGF-β表达水平高于健康人群，NK细胞PD-1、CD94和IL-10表达水平高于健康人群。HBV利用乙型肝炎表面抗原（HBsAg）通过MyD88/NFκB信号通路诱导具有HLA-E、PD-L1、IL-10和TGF-β表达的抑制性单核细胞。hbv处理的单核细胞通过PD-L1和HLA-E信号诱导NK细胞产生IL-10。这种NK细胞抑制自体T细胞的活化。我们的研究结果揭示了免疫抑制级联，其中HBV产生抑制性单核细胞，其启动调节性NK细胞分化导致T细胞抑制。
Background and aims HBV infection represents a major health problem worldwide, but the immunological mechanisms by which HBV causes chronic persistent infection remain only partly understood. Recently, cell subsets with suppressive features have been recognised among monocytes and natural killer (NK) cells. Here we examine the effects of HBV on monocytes and NK cells. Methods Monocytes and NK cells derived from chronic HBV-infected patients and healthy controls were purified and characterised for phenotype, gene expression and cytokines secretion by flow cytometry, quantitative real-time (qRT)-PCR, ELISA and western blotting. Culture and coculture of monocytes and NK cells were used to determine NK cell activation, using intracellular cytokines staining. Results In chronic HBV infection, monocytes express higher levels of PD-L1, HLA-E, interleukin (IL)-10 and TGF-β, and NK cells express higher levels of PD-1, CD94 and IL-10, compared with healthy individuals. HBV employs hepatitis B surface antigen (HBsAg) to induce suppressive monocytes with HLA-E, PD-L1, IL-10 and TGF-β expression via the MyD88/NFκB signalling pathway. HBV-treated monocytes induce NK cells to produce IL-10, via PD-L1 and HLA-E signals. Such NK cells inhibit autologous T cell activation. Conclusions Our findings reveal an immunosuppressive cascade, in which HBV generates suppressive monocytes, which initiate regulatory NK cells differentiation resulting in T cell inhibition.
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DOI：
10.1084/jem.20061287
发表时间：
2007-03-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Dunn C;Brunetto M;Reynolds G;Christophides T;Kennedy PT;Lampertico P;Das A;Lopes AR;Borrow P;Williams K;Humphreys E;Afford S;Adams DH;Bertoletti A;Maini MK
通讯作者：
Maini MK
影响因子：
4.4
作者：
Maier, Holly;Isogawa, Masanori;Chisari, Francis V.
通讯作者：
Chisari, Francis V.
影响因子：
20.3
作者：
Mori, N;Yamada, Y;Fujii, M
通讯作者：
Fujii, M
影响因子：
32.4
作者：
Cros J;Cagnard N;Woollard K;Patey N;Zhang SY;Senechal B;Puel A;Biswas SK;Moshous D;Picard C;Jais JP;D'Cruz D;Casanova JL;Trouillet C;Geissmann F
通讯作者：
Geissmann F
乙型肝炎表面抗原对单核细胞骨髓源性抑制细胞的极化是通过 ERK/IL-6/STAT3 信号反馈介导的，并抑制慢性乙型肝炎病毒感染中 T 细胞的激活
影响因子：
4.4
作者：
Fang, Zhong;Li, Jin;Yuan, Zhenghong
通讯作者：
Yuan, Zhenghong