Dynamic Perturbations of CD4 and CD8 T Cell Receptor Repertoires in Chronic Hepatitis B Patients upon Oral Antiviral Therapy.
Dynamic Perturbations of CD4 and CD8 T Cell Receptor Repertoires in Chronic Hepatitis B Patients upon Oral Antiviral Therapy.
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DOI：
10.3389/fimmu.2017.01142
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发表时间：
2017
影响因子：
7.3
通讯作者：
Wang Z
中科院分区：
文献类型：
--
作者：
Xu Y;Liu Y;Zhao M;Chen Y;Xie C;Gong M;Deng H;Li X;Sun J;Hou J;Wu H;Wang Z
长期使用核糖核酸类似物(Nucs)可以改善慢性乙型肝炎(CHB)患者的抗病毒T细胞应答。在导致乙肝e抗原(HBeAg)血清转换的早期阶段，Nucs是否以及在多大程度上改善了T细胞反应，仍有待阐明。根据52周的HBeAg血清转换，共有22名接受以替比夫定为基础的2年治疗的CHB患者入选，其中10人表现为完全应答(CR)，12人表现为非完全应答(NCR)。分别在基线、12周和24周对外周血中的CD4+和CD8+T细胞进行分类。T细胞受体β链(TcRβ)互补决定区3采用无偏高通量测序方法进行分析。与非缓解组相比，缓解组患者CD_4、CD_8亚群持续克隆率显著降低(P <； 0.001)，而新扩增克隆率显著升高(P <； 0.05)。患者的CD4T细胞比CD8细胞表现出更强的反应性。新的和扩大的克隆类型的数量与病毒抗原的下降呈负相关。总之，在治疗的早期阶段，基于NUC的治疗诱导了广泛而有力的T细胞反应，抗原血症迅速下降。T细胞的广泛扩增对HBeAg血清转换至关重要。我们的发现表明，NUC单一疗法有效地抑制乙肝病毒复制，辅以额外的免疫调节策略，可能会增加未来治愈CHB的可能性。
Long-term treatment with nucleos(t)ide analogs (NUCs) can improve the antiviral T cell response in chronic hepatitis B (CHB) patients. Whether and to what extent the T cell response is improved by NUCs in the early stage leading to hepatitis B e antigen (HBeAg) seroconversion remain to be clarified. A total of 22 CHB patients undergoing 2-year telbivudine-based therapy were enrolled, including 10 exhibiting a complete response (CR) and 12 exhibiting a non-complete response (NCR) according to HBeAg seroconversion at week 52. Peripheral CD4+ and CD8+ T cells were sorted at baseline, weeks 12, and 24. The T cell receptor β chain (TCRβ) complementarity-determining region 3 was analyzed by unbiased high-throughput sequencing. Compared with NCR group, patients in CR group had a much lower percentage of persistent clonotypes (P < 0.001) but remarkably higher percentages of new and expanded clonotypes (P < 0.05) between any two time points for both CD4 and CD8 subsets. The CD4 T cells exhibited a stronger response than CD8 population in the patients. The number of new and expanded clonotypes was inversely associated with the decline of viral antigen. In conclusion, NUC-based therapy induces a broad and vigorous T cell response with rapid decline of antigenemia during the early stage of treatment. A broad T cell expansion is crucial for HBeAg seroconversion. Our findings suggest that the potent suppression of hepatitis B virus replication by NUC monotherapy complemented with additional immunomodulatory strategies may increase the likelihood of a functional cure for CHB in the future.
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高通量 T 细胞受体测序揭示了 HBV 相关 HCC 中肿瘤组织和邻近非肿瘤组织之间的独特特性
影响因子：
7.2
作者：
Chen, Yunqing;Xu, Ying;Wang, Zhanhui
通讯作者：
Wang, Zhanhui
影响因子：
13.5
作者：
Lee, Hyun Woong;Lee, Heon Ju;Han, Kwang-Hyub
通讯作者：
Han, Kwang-Hyub
慢性丙型肝炎病毒和丙型肝炎病毒感染的抗病毒治疗的免疫学方面。
DOI：
10.1002/hep.27323
发表时间：
2015-02
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
Rehermann B;Bertoletti A
通讯作者：
Bertoletti A
影响因子：
10.7
作者：
Kumar, Sudhir;Stecher, Glen;Tamura, Koichiro
通讯作者：
Tamura, Koichiro
影响因子：
29.4
作者：
Park JJ;Wong DK;Wahed AS;Lee WM;Feld JJ;Terrault N;Khalili M;Sterling RK;Kowdley KV;Bzowej N;Lau DT;Kim WR;Smith C;Carithers RL;Torrey KW;Keith JW;Levine DL;Traum D;Ho S;Valiga ME;Johnson GS;Doo E;Lok AS;Chang KM;Hepatitis B Research Network
通讯作者：
Hepatitis B Research Network