中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Issue 6
Jun.  2014
Turn off MathJax
Article Contents

Changes in NK cells and regulatory T cells among patients with refractory chronic hepatitis C during antiviral treatment

DOI: 10.3969/j.issn.1001-5256.2014.06.008
Research funding:

 

  • Received Date: 2013-08-20
  • Published Date: 2014-06-20
  • Objective To investigate the changes in NK cells and regulatory T ( Treg) cells among patients with refractory chronic hepatitis C ( CHC) during antiviral therapy and to analyze antiviral effect-related immunological factors. Methods A total of 41 patients with refractory CHC ( 30 treatment- naive patients and 11 treatment- unresponsive patients) and 11 healthy controls ( HC) were enrolled in this prospective open cohort study. Naive patients received pegylated interferon α- 2a ( Peg- IFN- α- 2a) 180 μg /week and ribavirin ( RBV) 10. 6- 15mg / kg /day for 48 weeks, while unresponsive patients received Peg- IFN- α- 2a 180 μg /week and RBV 15 mg /kg /day for 72 weeks. Blood cells and serum were dynamically collected to measure HCV RNA, liver function, NK cells and Treg cells and to analyze curative effect- related immunological factors. Continuous variables were analyzed by t- test or rank sum test, and discrete variables were analyzed by chi- square test. Results All patients finished antiviral treatment and 24- week follow- up survey. Seventeen naive patients ( 56. 7%) and 3 unresponsive patients ( 27. 2%) achieved a sustained virologic response ( SVR) . The 8 unresponsive patients without SVR were named response- free patients ( RFP) . At baseline, the percentage of NK cells in patients was lower than that in the HC group, while the percentage of Treg cells in patients was higher than that in the HC group. During antiviral therapy, in naive patients with SVR, the percentage of NK cells increased at week 24 of treatment, as compared with the baseline and week 4, and the percentage of Treg cells decreased at week 24, as compared with the baseline and week 4; In naive patients without SVR, the percentage of Treg cells increased at week 24, as compared with the baseline and week 4; no significant change in the percentage of NK cells or Treg cells was observed in unresponsive patients without SVR.Conclusion Decrease in NK cells and increase in Treg cells are related to chronic HCV infection. Dynamic changes in NK cells and Treg cells can predict the efficacy of antiviral therapy: the increase in NK cells and decrease in Treg cells, which are indicative of upregulation immune function and downregulation of immunosuppression, can be used for predicting SVR.

     

  • loading
  • [1] World Health Organization.Global surveillance and control of hepatitis C.Report of a WHO Consultation organized in collaboration with the Viral Hepatitis Prevention Board, Antwerp, Belgium[J].J Viral Hepat, 1999, 6 (1) :35-47.
    [2] CHEN YS, LI L, CUI FQ, et al.A sero-epidemiological study on hepatitis C in China[J].Chin J Epidemiol, 2011, 32 (9) :888-891. (in Chinese) 陈园生, 李黎, 崔富强, 等.中国丙型肝炎血清流行病学研究[J].中华流行病学杂志, 2011, 32 (9) :888-891.
    [3]XIE Y, XU DZ, LU ZM, et al.The influence of HCV genotype on the IFN treatment of patients with chronic C[J].Chin J Hepatol, 2004, 12 (2) :72-75. (in Chinese) 谢尧, 徐道振, 陆志檬, 等.HCV基因型对慢性丙型肝炎干扰素疗效的影响[J].中华肝脏病杂志, 2004, 12 (2) :72-75.
    [4]XU B, LYU P, ZHU M.Epidemiological aspects of the genotype of hepatitis C virus[J].Chin J Exp Clin Virol, 2000, 14 (2) :148-150. (in Chinese) 徐蓓, 吕屏, 朱玫.慢性丙型肝炎患者HCV基因型调查[J].中华实验和临床病毒学杂志, 2000, 14 (2) :148-150.
    [5]YAN Y, LI Z, GUO XH, et al.A study on HCV-RNA quantitative detection and genotype in Peking[J].J Med Theory Pract, 2007, 20 (7) :756-757. (in Chinese) 严艳, 李卓, 郭向华, 等.北京地区慢性丙型肝炎患者血清HCV-RNA定量检测与基因分型的研究[J].医学理论与实践, 2007, 20 (7) :756-757.
    [6] HADZIYANNIS SJ, SETTE H JR, MORGAN TR, et al.Peginterferon-alpha 2a and ribavirin combination therapy in chronic hepatitis C:a randomized study of treatment duration and ribavirin dose[J].Ann Intern Med, 2004, 140 (5) :346-355.
    [7]AFDHAL NH.The natural history of hepatitis C[J].Semin Liver Dis, 2004, 24 (Suppl 2) :3-8.
    [8] GHANY MG, STRADER DB, THOMAS DL, et al.Diagnosis, management, and treatment of hepatitis C:an update[J].Hepatology, 2009, 49 (4) :1335-1374.
    [9]SHERMAN M, SHAFRAN S, BURAK K, et al.Management of chronic hepatitis C:consensus guidelines[J].Can J Gastroenterol, 2007, 21 (Suppl C) :25C-34C.
    [10]Chinese Society of Hepatology and Chinese Society of Infectious Diseases and Parasitology, Chinese Medical Association.Guidelines for prevention and treatment of hepatitis C[J].J Clin Hepatol, 2004, 20 (4) :197-203. (in Chinese) 中华医学会肝病学分会、传染病与寄生虫病学分会.丙型肝炎防治指南[J].临床肝胆病杂志, 2004, 20 (4) :197-203.
    [11]SAKAGUCHI S, SAKAGUCHI N, ASANO M, et al.Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25) .Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases[J].J Immunol, 1995, 155 (3) :1151-1164.
    [12] HORI S, NOMURA T, SAKAGUCHI S.Control of regulatory T cell development by the transcription factor Foxp3[J].Science, 2003, 299 (5609) :1057-1061.
    [13] CALIGIURI M.Human nature killer cell[J].J Blood, 2008, 112 (3) :461-469.
    [14] POLI A, MICHEL T, THRESINE M, et al.CD56bright natural killer (NK) cells:An important NK cell subset[J].Immunology, 2009, 126 (4) :458-465.
    [15]MORETTA L, FERLAZZO G, BOTTINO C, et al.Effector and regulatory events during natural killer-dendritic cell interactions[J].Immunol Rev, 2006, 214 (1) :219-228.
    [16]DESSOUKI O, KAMIYA Y, NAGAHAMA H, et al.Chronic hepatitis C viral infection reduces NK cell frequency and suppresses cytokine secretion:Reversion byanti-viral treatment[J].Biochem Biophys Res Commun, 2010, 393 (2) :331-337.
    [17]AMADEI B, URBANI S, CAZALY A, et al.Activation of natural killer cells during acute infection with hepatitis C virus[J].Gastroenterology, 2010, 138 (4) :1536-1545.
    [18]MORISHIMA C, PASCHAL DM, WANG CC, et al.Decreased NK cell frequency in chronic hepatitis C does not affect ex vivo cytolytic killing[J].Hepatology, 2006, 43 (3) :573-580.
    [19]LIN AW, GONZALEZ SA, CUNNINGHAM-RUNDLES S, et al.CD56 (+dim) and CD56 (+bright) cell activation and apoptosis in hepatitis C virus infection[J].Clin Exp Immunol, 2004, 137 (2) :408-416.
    [20] YOSHIZAWA K, ABE H, KUBO Y, et al.Expansion of CD4 (+) CD25 (+) FoxP3 (+) regulatory T cells in hepatitis C virus-related chronic hepatitis, cirrhosis and hepatocellular carcinoma[J].Hepatol Res, 2010, 40 (2) :179-187.
    [21]BOLACCHI F, SINISTRO A, CIAPRINI C, et al.Increased hepatitis C virus (HCV) -specific CD4+CD25+regulatory T lymphocytes and reduced HCV-specific CD4+T cell response in HCVinfected patients with normal versus abnormal alanine aminotransferase levels[J].Clin Exp Immunol, 2006, 144 (2) :188-196.
    [22]TERME M, CHAPUT N, COMBADIERE B, et al.Regulatory T cells control dendritic cell/NK cell cross-talk in lymph nodes at the steady state by inhibiting CD4+self-reactive T cells[J].J Immunol, 2008, 180 (7) :4679-4686.
    [23]LEE S, WATSON MW, FLEXMAN JP, et al.Increased proportion of the CD56 (bright) NK cell subset in patients chronically infected with hepatitis C virus (HCV) receiving interferon-alpha and ribavirin therapy[J].J Med Virol, 2010, 82 (4) :568-574.
    [24]BURTON JR, KLARQUIST J, IM K, et al.Prospective analysis of effector and regulatory CD4+T cells in chronic HCV patients undergoing combination antiviral therapy[J].J Hepatol, 2008, 49 (3) :329-338.
    [25]LEE S, HAMMOND T, WATSON MW, et al.Could a loss of memory T cells limit responses to hepatitis C virus (HCV) antigens in blood leucocytes frompatients chronically infected with HCV before and during pegylated interferon-alpha and ribavirin therapy?[J].Clin Exp Immunol, 2010, 161 (1) :118-126.
    [26]SOLDEVILA B, ALONSO N, MARTíNEZ-ARCONADA MJ, et al.A prospective study of T-and B-lymphocyte subpopulations, CD81 expression levels on B cells and regulatory CD4 (+) CD25 (+) CD127 (low/-) FoxP3 (+) T cells in patients with chronic HCV infection during pegylated interferon-alpha 2a plus ribavirin treatment[J].J Viral Hepat, 2011, 18 (6) :384-392.
    [27]FRANCESCHINI D, PAROLI M, FRANCAVILLA V, et al.PDL1 negatively regulates CD4+CD25+Foxp3+Tregs by limiting STAT-5 phosphorylation in patients chronicallyinfected with HCV[J].J Clin Invest, 2009, 119 (3) :551-564.
    [28]AKIYAMA M, ICHIKAWA T, MIYAAKI H, et al.Relationship between regulatory T cells and the combination of pegylated interferon and ribavirin for the treatment of chronic hepatitis type C[J].Intervirology, 2010, 53 (3) :154-160.
    [29]TSENG KC, HO YC, HSIEH YH, et al.Elevated frequency and function of regulatory T cells in patients with active chronic hepatitis C[J].J Gastroenterol, 2012, 47 (7) :823-833.
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Article Metrics

    Article views (3118) PDF downloads(658) Cited by()
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return