IL-10-producing regulatory B-cells suppressed effector T-cells but enhanced regulatory T-cells in chronic HBV infection
IL-10-producing regulatory B-cells suppressed effector T-cells but enhanced regulatory T-cells in chronic HBV infection
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在慢性 HBV 感染中，产生 IL-10 的调节性 B 细胞抑制效应 T 细胞，但增强调节性 T 细胞
DOI：
10.1042/cs20160069
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发表时间：
2016-06-01
期刊：
影响因子：
6
通讯作者：
Jiang, Wei
中科院分区：
文献类型：
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作者：
Liu, Yun;Cheng, Li-sha;Jiang, Wei
在慢性乙型肝炎病毒（HBV）感染期间，机体对抗原的非特异性免疫反应已被证实有所增强。在此，我们评估了产生白细胞介素 - 10（IL - 10）的调节性B细胞（Bregs）在HBV相关肝纤维化（HBV - LF）发病机制中的作用，并对其免疫调节效应进行了评估。本研究纳入了67例慢性乙型肝炎（CHB）患者。对患者外周血B细胞（记忆性CD19⁺CD24高表达CD27⁺细胞、未成熟/过渡型CD19⁺CD24高表达CD38高表达细胞、成熟CD19⁺CD24中等表达CD38中等表达细胞）的数量和频率进行了检测与分析。通过流式细胞术分选CD4⁺ T细胞，并与自体Bregs共同培养，以阐明Bregs对CD4⁺ T细胞（包括效应T细胞和调节性T细胞（Tregs））的影响。同时，还对Bregs潜在的免疫调节机制进行了研究。CHB患者体内总B细胞和Bregs的数量增多。Bregs的频率与丙氨酸氨基转移酶（ALT）升高及组织学炎症分级（G）呈负相关，但与组织学纤维化分期（S）进展及HBV复制增强呈正相关。Bregs的表型主要为CD19⁺CD24高表达CD38高表达。与Bregs共培养时，CHB患者的CD4⁺CD25⁻T细胞相较于单独培养的CD4⁺CD25⁻T细胞，产生的干扰素 - γ（IFN - γ）和IL - 17减少，但产生的IL - 4增多，同时其向Tregs和IL - 10⁺ T细胞的转化增强。此外，去除CHB样本中的Bregs会显著降低Tregs数量以及细胞毒性T淋巴细胞相关抗原 - 4（CTLA - 4）、IL - 10和转化生长因子 - β（TGF - β）的表达。而且，观察到的调节作用部分依赖于IL - 10的释放以及细胞间的接触。增多的Bregs可抑制效应T细胞功能，但增强Tregs功能，这可能会影响慢性HBV感染中的免疫耐受。
Non-specific immune responses to antigens have been demonstrated as being enhanced during chronic hepatitis B virus (HBV) infection. Here, we evaluated the role of interleukin-10 (IL-10)-producing regulatory B-cells (Bregs) in the pathogenesis of HBV-related liver fibrosis (HBV-LF) and assessed their immunoregulatory effects. Sixty-seven patients diagnosed with chronic hepatitis B (CHB) were enrolled in this study. Numbers and frequencies of peripheral B-cells (memory CD19(+)CD24(hi)CD27(+) cells, immature/transitional CD19(+)CD24(hi)CD38(hi) cells, mature CD19(+)CD24(int)CD38(int) cells) were tested and analysed. Flow cytometry-sorted CD4(+) T cells were cultured with autologous Bregs to elucidate the effects of Bregs on CD4(+) T cells, including effector T and regulatory T-cells (Tregs). The potential immunoregulatory mechanism of Bregs was also investigated. The numbers of total B-cells and Bregs were enriched in CHB patients. The frequency of Bregs was negatively correlated with elevated alanine aminotransferase (ALT) and histological inflammation grades (G), but positively correlated with advanced histological fibrosis stages (S) and enhanced HBV replication. The phenotype of Bregs was predominantly characterized as CD19(+)CD24(hi)CD38(hi). In co-culture with Bregs, CD4(+)CD25(-)T cells from CHB patients produced less interferon-gamma (IFN-gamma) and IL-17 but more IL-4 than CD4(+) CD25-T cells alone, whereas their conversions into Tregs and IL-10(+) T cells were enhanced. In addition, Breg depletion in CHB samples dramatically decreased Treg numbers and expression of cytotoxic T-lymphocyte associated antigen-4 (CTLA-4), IL-10 and transforming growth factor-beta (TGF-beta). Moreover, the observed regulatory effect was partly dependent on IL-10 release and cell-to-cell contact. Elevated Bregs can suppress effector T but enhance Treg functions, which might influence immune tolerance in chronic HBV infection.