IL-10-producing regulatory B cells in the pathogenesis of chronic hepatitis B virus infection.
IL-10-producing regulatory B cells in the pathogenesis of chronic hepatitis B virus infection.
复制标题
DOI：
10.4049/jimmunol.1103139
复制
发表时间：
2012-10-15
期刊：
影响因子：
--
通讯作者：
Maini MK
中科院分区：
文献类型：
--
作者：
Das A;Ellis G;Pallant C;Lopes AR;Khanna P;Peppa D;Chen A;Blair P;Dusheiko G;Gill U;Kennedy PT;Brunetto M;Lampertico P;Mauri C;Maini MK
已发现B细胞的调节亚群调节自身免疫、感染和癌症中的免疫应答，但尚未在人类持续性病毒感染的情况下进行研究。IL-10在慢性B型肝炎病毒感染（CH B）3患者中升高，但其细胞来源和对抗病毒T细胞的影响尚未得到解决。我们研究了IL-10和调节性B细胞在CH B发病机制中的作用。在经历自发疾病发作的CHB患者中纵向研究血清IL-10水平。IL-10水平与病毒载量或肝脏炎症的波动之间存在密切的时间相关性。IL-10的体外阻断挽救了多功能病毒特异性CD 8 T细胞应答。为了研究调节性B细胞的潜在贡献，直接离体和暴露于与HBV相关的刺激物（CpG或HBV抗原）后测量它们的频率。产生IL-10的B细胞在患者中富集，并且它们的频率在刺激后和直接离体时与肝耀斑时间相关。表型上，这些细胞主要是离体未成熟的（CD 19 + CD 24 hiCD 38 hi）;分选的CD 19 + CD 24 hiCD 38 hi细胞以IL-10依赖性方式抑制HBV特异性CD 8 T细胞应答。总之，这些数据揭示了一种新型的产生IL-10的B细胞亚群，能够调节CH B中的T细胞免疫。
A regulatory subset of B cells has been found to modulate immune responses in autoimmunity, infection and cancer but has not been investigated in the setting of human persistent viral infection. IL-10 is elevated in patients with chronic hepatitis B virus infection (CHB)3 but its cellular sources and impact on antiviral T cells have not been addressed. We investigated the role of IL-10 and regulatory B cells in the pathogenesis of CHB. Serum IL-10 levels were studied longitudinally in patients with CHB undergoing spontaneous disease flares. There was a close temporal correlation between IL-10 levels and fluctuations in viral load or liver inflammation. Blockade of IL-10 in vitro rescued polyfunctional virus-specific CD8 T cell responses. To investigate the potential contribution of regulatory B cells, their frequency was measured directly ex vivo and after exposure to stimuli relevant to HBV (CpG or HBV antigens). IL-10-producing B cells were enriched in patients, and their frequency correlated temporally with hepatic flares, both after stimulation and directly ex vivo. Phenotypically, these cells were predominantly immature (CD19+CD24hiCD38hi) ex vivo; sorted CD19+CD24hiCD38hi cells suppressed HBV-specific CD8 T cell responses in an IL-10-dependent manner. In summary, these data reveal a novel IL-10-producing subset of B cells able to regulate T cell immunity in CHB.
登录
查看更多内容
巨细胞病毒利用了唾液腺中IL-10介导的免疫调节。
影响因子：
15.3
作者：
Humphreys, Ian R;de Trez, Carl;Kinkade, April;Benedict, Chris A;Croft, Michael;Ware, Carl F
通讯作者：
Ware, Carl F
影响因子：
15.3
作者：
Das, Abhishek;Hoare, Matthew;Davies, Nathan;Lopes, A. Ross;Dunn, Claire;Kennedy, Patrick T. F.;Alexander, Graeme;Finney, Helene;Lawson, Alistair;Plunkett, Fiona J.;Bertoletti, Antonio;Akbar, Arne N.;Maini, Mala K.
通讯作者：
Maini, Mala K.
影响因子：
4.4
作者：
Lampropoulou, Vicky;Hoehlig, Kai;Fillatreau, Simon
通讯作者：
Fillatreau, Simon
影响因子：
13.5
作者：
Dhirapong, Amy;Lleo, Ana;Yang, Guo-Xiang;Tsuneyama, Koichi;Dunn, Robert;Kehry, Marilyn;Packard, Thomas A.;Cambier, John C.;Liu, Fu-Tong;Lindor, Keith;Coppel, Ross L.;Ansari, Aftab A.;Gershwin, M. Eric
通讯作者：
Gershwin, M. Eric
影响因子：
5.4
作者：
Barr, Tom A;Brown, Sheila;Ryan, Gemma;Zhao, Jiexin;Gray, David
通讯作者：
Gray, David