IFN-α-2b sensitizes non-responders of hepatitis B to interleukin-2
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- 英文论文题名：IFN-α-2b sensitizes non-responders of hepatitis B to interleukin-2
- 论文作者：Wang Dongyao ; Fu Binqing ; Shen Xiaokun ; Liu Yanyan ; Guo Chuang ; Sun Rui ; Li Jiabin ; Tian Zhigang ; Wei Haiming
- 英文论文作者：Wang Dongyao ; Fu Binqing ; Shen Xiaokun ; Liu Yanyan ; Guo Chuang ; Sun Rui ; Li Jiabin ; Tian Zhigang ; Wei Haiming ; Institute of Immunology and The CAS Key Laboratory of Innate Immunity and Chronic Disease ; School of Life Science and Medical Center ; University of Science and Technology of China ; Hefei National Laboratory for Physical Sciences at Microscale ; University of Science and Technology of China ; Department of Infectious Diseases ; the First Affiliated Hospital of Anhui Medical University
- 年：2016
- 作者机构：Institute of Immunology and The CAS Key Laboratory of Innate Immunity and Chronic Disease,School of Life Science and Medical Center,University of Science and Technology of China;Hefei National Laboratory for Physical Sciences at Microscale,University of Science and Technology of China;Department of Infectious Diseases,the First Affiliated Hospital of Anhui Medical University;
- 英文论文关键词：Hepatitis B virus(HBV) ; Interleukin(IL)-2 ; Non-responders ; NK cells ; Treg cells
- 会议召开时间：2016-11-04
- 会议录名称：第十一届全国免疫学学术大会摘要汇编
- 英文会议录名称：Abstracts of 2016 CSI Congress on Immunology
- 语种：英文
- 分类号：R512.62
- 学会代码：IGMD
- 会议名称：第十一届全国免疫学学术大会
- 会议地点：中国安徽合肥
- 主办单位：中国免疫学会
- 学会名称：中国免疫学会
- 页数：1
- 文件大小：1343k
- 原文格式：D
- 会议级别：全国
摘要
Background: More than 60% of patients infected with hepatitis B virus(HBV) experience a diminished HBV virologic response to standard pegylated(peg) IFN-α-2b based therapies and are regarded as non-response(NR) patients. Methods: Here we explored a novel strategy of anti-HBV therapy in the 6-32 week interval after standard peg-IFN-α-2b therapy. Peripheral blood mononuclear cells(PBMC) from these NR patients progressed to sequential low dose of interleukin(IL)-2 stimulation. Results: We demonstrated that peg-IFN-α-2b could prime the immune system of non-responders to IL-2. The expansion in proliferating, activatory receptors and functional NK and T cells was more pronounced following sequential IL-2 than treated with peg-IFN-α-2b only. Meanwhile, the treatment of peg-IFN-α-2b down-regulated the expression of high-affinity heterotrimeric IL-2Rαβγ on CD8~+T cells and the phosphorylation of STAT5, so that the transcription of Foxp3 and the proportion of regulatory T(Treg) cells would not increase due to subsequent stimulation of IL-2. However, for the patients completed peg-IFN-α-2b therapy more than 1 year, the peg-IFN-α-2b priming seemed invalid. And the expression of inhibitory molecule Tim-3 on NK cells significantly increased after the sequential stimulation of IL-2. Conclusion: Thus, our findings may be applied to design effective and promising strategies for restoring anti-HBV immunity of NR patients in no more than 1 year after the end of standard peg-IFN-α-2b therapy, and to identify a novel therapeutic window for hepatitis B patients.
Background: More than 60% of patients infected with hepatitis B virus(HBV) experience a diminished HBV virologic response to standard pegylated(peg) IFN-α-2b based therapies and are regarded as non-response(NR) patients. Methods: Here we explored a novel strategy of anti-HBV therapy in the 6-32 week interval after standard peg-IFN-α-2b therapy. Peripheral blood mononuclear cells(PBMC) from these NR patients progressed to sequential low dose of interleukin(IL)-2 stimulation. Results: We demonstrated that peg-IFN-α-2b could prime the immune system of non-responders to IL-2. The expansion in proliferating, activatory receptors and functional NK and T cells was more pronounced following sequential IL-2 than treated with peg-IFN-α-2b only. Meanwhile, the treatment of peg-IFN-α-2b down-regulated the expression of high-affinity heterotrimeric IL-2Rαβγ on CD4+T cells and the phosphorylation of STAT5, so that the transcription of Foxp3 and the proportion of regulatory T(Treg) cells would not increase due to subsequent stimulation of IL-2. However, for the patients completed peg-IFN-α-2b therapy more than 1 year, the peg-IFN-α-2b priming seemed invalid. And the expression of inhibitory molecule Tim-3 on NK cells significantly increased after the sequential stimulation of IL-2. Conclusion: Thus, our findings may be applied to design effective and promising strategies for restoring anti-HBV immunity of NR patients in no more than 1 year after the end of standard peg-IFN-α-2b therapy, and to identify a novel therapeutic window for hepatitis B patients.
Background: More than 60% of patients infected with hepatitis B virus(HBV) experience a diminished HBV virologic response to standard pegylated(peg) IFN-α-2b based therapies and are regarded as non-response(NR) patients. Methods: Here we explored a novel strategy of anti-HBV therapy in the 6-32 week interval after standard peg-IFN-α-2b therapy. Peripheral blood mononuclear cells(PBMC) from these NR patients progressed to sequential low dose of interleukin(IL)-2 stimulation. Results: We demonstrated that peg-IFN-α-2b could prime the immune system of non-responders to IL-2. The expansion in proliferating, activatory receptors and functional NK and T cells was more pronounced following sequential IL-2 than treated with peg-IFN-α-2b only. Meanwhile, the treatment of peg-IFN-α-2b down-regulated the expression of high-affinity heterotrimeric IL-2Rαβγ on CD4+T cells and the phosphorylation of STAT5, so that the transcription of Foxp3 and the proportion of regulatory T(Treg) cells would not increase due to subsequent stimulation of IL-2. However, for the patients completed peg-IFN-α-2b therapy more than 1 year, the peg-IFN-α-2b priming seemed invalid. And the expression of inhibitory molecule Tim-3 on NK cells significantly increased after the sequential stimulation of IL-2. Conclusion: Thus, our findings may be applied to design effective and promising strategies for restoring anti-HBV immunity of NR patients in no more than 1 year after the end of standard peg-IFN-α-2b therapy, and to identify a novel therapeutic window for hepatitis B patients.
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