中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R

留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码

慢性HBV感染者病毒特异性T淋巴细胞:耗竭还是沉默?

王昊亮 邓国宏

引用本文:
Citation:

慢性HBV感染者病毒特异性T淋巴细胞:耗竭还是沉默?

DOI: 10.3969/j.issn.1001-5256.2020.05.005
基金项目: 

传染病国家科技重大专项(2018ZX10302206); 国家自然科学基金重点项目(81930061); 重庆市自然科学基金(cstc2019jcyj-zdxmX0004,cstc2019jcyj-bshX0039); 

详细信息
  • 中图分类号: R512.62

Functional status of hepatitis B virus-specific T cells in patients with chronic hepatitis B virus infection:Exhausted or silenced?

Research funding: 

 

  • 摘要:

    当前主流观点认为,慢性HBV感染者的病毒特异性T淋巴细胞是处于耗竭状态的T淋巴细胞。总结了以往研究支持该假说的证据,同时对于该假说与临床观察不一致之处提出相应的疑问。综合近期研究结果,认为慢性HBV感染者的病毒特异性T淋巴细胞很可能是分化早期的前体T淋巴细胞占主导,功能上处于沉默而非耗竭状态,并分析了该群T淋巴细胞保持沉默静息状态的可能原因。

     

  • [1] LIAW YF, CHU CM. Immune tolerance phase of chronic hepatitis B[J]. Gastroenterology, 2017, 152(5):1245-1246.
    [2] PENNA A, ARTINI M, CAVALLI A, et al. Long-lasting memory T cell responses following self-limited acute hepatitis B[J]. J Clin Invest, 1996, 98(5):1185-1194.
    [3] REHERMANN B, FOWLER P, SIDNEY J, et al. The cytotoxic T lymphocyte response to multiple hepatitis B virus polymerase epitopes during and after acute viral hepatitis[J]. J Exp Med,1995, 181(3):1047-1058.
    [4] FERRARI C, PENNA A, BERTOLETTI A, et al. Cellular immune response to hepatitis B virus-encoded antigens in acute and chronic hepatitis B virus infection[J]. J Immunol,1990, 145(10):3442-3449.
    [5] THIMME R, WIELAND S, STEIGER C, et al. CD8(+)T cells mediate viral clearance and disease pathogenesis during acute hepatitis B virus infection[J]. J Virol, 2003, 77(1):68-76.
    [6] BONI C, FISICARO P, VALDATTA C, et al. Characterization of hepatitis B virus(HBV)-specific T-cell dysfunction in chronic HBV infection[J]. J Virol, 2007, 81(8):4215-4225.
    [7] BENGSCH B, MARTIN B, THIMME R. Restoration of HBVspecific CD8+T cell function by PD-1 blockade in inactive carrier patients is linked to T cell differentiation[J]. J Hepatol,2014, 61(6):1212-1219.
    [8] SCHURICH A, KHANNA P, LOPES AR, et al. Role of the coinhibitory receptor cytotoxic T lymphocyte antigen-4 on apoptosis-Prone CD8 T cells in persistent hepatitis B virus infection[J]. Hepatology, 2011, 53(5):1494-1503.
    [9] LOPES AR, KELLAM P, DAS A, et al. Bim-mediated deletion of antigen-specific CD8 T cells in patients unable to control HBV infection[J]. J Clin Invest, 2008, 118(5):1835-1845.
    [10] PARK JJ, WONG DK, WAHED AS, et al. Hepatitis B virusspecific and global T-cell dysfunction in chronic hepatitis B[J]. Gastroenterology, 2016, 150(3):684-695. e5.
    [11] WHERRY EJ. T cell exhaustion[J]. Nature Immunol, 2011,12:492-499.
    [12] MUELLER SN, AHMED R. High antigen levels are the cause of T cell exhaustion during chronic viral infection[J]. Proc Natl Acad Sci U S A, 2009, 106(21):8623-8628.
    [13] KENNEDY P, SANDALOVA E, JO J, et al. Preserved T-cell function in children and young adults with immune-tolerant chronic hepatitis B[J]. Gastroenterology, 2012, 143(3):637-645.
    [14] WHERRY EJ, BLATTMAN JN, MURALI-KRISHNA K, et al.Viral persistence alters CD8 T-cell immunodominance and tissue distribution and results in distinct stages of functional impairment[J]. J Virol, 2003, 77(8):4911-4927.
    [15] BROOKS DG, TEYTON L, OLDSTONE MB, et al. Intrinsic functional dysregulation of CD4 T cells occurs rapidly fol owing persistent viral infection[J]. J Virol, 2005, 79(16):10514-10527.
    [16] RIVINO L, LE BERT N, GILL US, et al. Hepatitis B virus-specific T cells associate with viral control upon nucleos(t)ide-analogue therapy discontinuation[J]. J Clin Invest, 2018, 128(2):668-681.
    [17] RINKER F, ZIMMER CL, HÖNER ZU SIEDERDISSEN C, et al.Hepatitis B virus-specific T cell responses after stopping nucleos(t)ide analogue therapy in HBeAg-negative chronic hepatitis B[J]. J Hepatol, 2018, 69(3):584-593.
    [18] TSAI SL, CHEN PJ, LAI MY, et al. Acute exacerbations of chronic type B hepatitis are accompanied by increased T cell responses to hepatitis B core and e antigens. Implications for hepatitis B e antigen seroconversion[J]. J Clin Invest, 1992,89(1):87-96.
    [19] WANG H, LUO H, WAN X, et al. TNF-α/IFN-γprofile of HBV-specific CD4 T cells is associated with liver damage and viral clearance in chronic HBV infection[J]. J Hepatol, 2020,72(1):45-56.
    [20] VERDON D, BROOKS A, GAGGAR A, et al. Immunological assessment of HBeAg-negative chronic hepatitis B patient responses following anti-PD-1 treatment[J]. Hepatology,2017, 66:23A.
    [21] CAO Z, LIU Y, MA L, et al. A potent hepatitis B surface antigen response in subjects with inactive hepatitis B surface antigen carrier treated with pegylated-interferon alpha[J]. Hepatology, 2017, 66(4):1058-1066.
    [22] IM SJ, HASHIMOTO M, GERNER MY, et al. Defining CD8+T cells that provide the proliferative burst after PD-1 therapy[J]. Nature, 2016, 537(7620):417-421.
    [23] JANSEN CS, PROKHNEVSKA N, MASTER VA, et al. An intratumoral niche maintains and differentiates stem-like CD8 T cel s[J]. Nature, 2019, 576(7787):465-470.
    [24] KURKTSCHIEV PD, RAZIORROUH B, SCHRAUT W, et al.Dysfunctional CD8+T cells in hepatitis B and C are characterized by a lack of antigen-specific T-bet induction[J]. J Exp Med, 2014, 211(10):2047-2059.
    [25] CRAWFORD A, ANGELOSANTO JM, KAO C, et al. Molecular and transcriptional basis of CD4+T cell dysfunction during chronic infection[J]. Immunity, 2014, 40(2):289-302.
    [26] WU JQ, SEAY M, SCHULZ VP, et al. Tcf7 is an important regulator of the switch of self-renewal and differentiation in a multipotential hematopoietic cell line[J]. PLoS Genet, 2012,8(3):e1002565.
    [27] ZHOU X, YU S, ZHAO DM, et al. Differentiation and persistence of memory CD8(+)T cells depend on T cell factor 1[J]. Immunity, 2010, 33(2):229-240.
    [28] SUSLOV A, BOLDANOVA T, WANG X, et al. Hepatitis B virus does not interfere with innate immune responses in the human liver[J]. Gastroenterology, 2018, 154(6):1778-1790.
    [29] VYAS AK, JINDAL A, TREHANPATI N. Ponder the innate immunity in hepatitis B infection[J]. Gastroenterology, 2018,155(4):1277.
    [30] TAN AT, KOH S, GOH W, et al. A longitudinal analysis of innate and adaptive immune profile during hepatic flares in chronic hepatitis B[J]. J Hepatol, 2010, 52(3):330-339.
    [31] JACOBI FJ, WILD K, SMITS M, et al. OX40 stimulation and PD-L1 blockade synergistically augment HBV-specific CD4T cells in patients with HBeAg-negative infection[J]. J Hepatol, 2019, 70(6):1103-1113.
  • 加载中
计量
  • 文章访问数:  967
  • HTML全文浏览量:  42
  • PDF下载量:  235
  • 被引次数: 0
出版历程
  • 出版日期:  2020-05-20
  • 分享
  • 用微信扫码二维码

    分享至好友和朋友圈

目录

    /

    返回文章
    返回