Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2012

Open Access 01-12-2012 | Research

Phenotypes and clinical significance of circulating CD4+CD25+ regulatory T cells (Tregs) in patients with acute-on-chronic liver failure (ACLF)

Authors: Jiezuan Yang, Ping Yi, Li Wei, Zherong Xu, Yunbo Chen, Lingling Tang, Lanjuan Li

Published in: Journal of Translational Medicine | Issue 1/2012

Login to get access

Abstract

Background

CD4+CD25+ regulatory T cells (Tregs) play an important role in maintaining immunological tolerance to self and foreign antigens. T cell receptors (TCR) reflect the composition and function of T cells. It is not universally agreed that there is a relationship between CD4+CD25+ Treg frequency and the severity of acute-on-chronic liver failure (ACLF). The repertoire of TCR beta chain variable (TCRBV) regions of peripheral Tregs in ACLF patients is not well understood.

Methods

Human PBMCs were separated and sorted into CD4+CD25+ Treg subsets using density gradient centrifugation and magnetic activated cell sorting (MACS). The CD4+CD25high Treg frequency in peripheral blood of ACLF and chronic hepatitis B (CHB) patients was measured by flow cytometry. The molecular profiles of TCRBV CDR3 were determined using gene melting spectral pattern (GMSP) analysis. TCRBV gene families were cloned and sequenced when the GMSP profiles showed a single-peak.

Results

CD4+CD25high Treg prevalence in peripheral blood of ACLF patients is increased significantly compared to healthy donors (HDs) (P < 0.01) and CHB patients (P < 0.01). The prevalence of CD4+CD25high Tregs in ACLF or CHB patients is positively correlated with HBV DNA load. The TCRBV11, BV13.1, BV18, BV20 are the most prevalent TCRBV in CD4+CD25+ Tregs in ACLF and CHB patients. In addition, the CDR3 motifs were relatively conserved in these four TCRBV gene families.

Conclusions

The CD4+CD25high Tregs prevalence in peripheral blood is indicative of disease severity in ACLF or CHB patients. The relatively conserved TCRBV20 CDR3 motif “TGTGHSPLH” and TCRBV11 CDR3 motif “VYNEQ” may be used in helping diagnosis and treat patients with ACLF.
Appendix
Available only for authorised users
Literature
1.
Lanini S, Puro V, Lauria FN, Fusco FM, Nisii C, Ippolito G: Patient to patient transmission of hepatitis B virus: a systematic review of reports on outbreaks between 1992 and 2007. BMC Med. 2009, 7: 15-10.1186/1741-7015-7-15.CrossRefPubMedPubMedCentral
2.
Wiersma ST, McMahon B, Pawlotsky JM, Thio CL, Thursz M, Lim SG, Ocama P, Esmat G, Maimuna M, Bell D, Vitoria M, Eramova I, Lavanchy D, Dusheiko G: Treatment of chronic hepatitis B virus infection in resource-constrained settings: expert panel consensus. Liver Int. 2011, 31: 755-761. 10.1111/j.1478-3231.2010.02373.x.CrossRefPubMed
3.
Xu Z, Ren X, Liu Y, Li X, Bai S, Zhong Y, Wang L, Mao P, Wang H, Xin S, Wong VW, Chan HL, Zoulim F, Xu D: Association of hepatitis B virus mutations in basal core promoter and precore regions with severity of liver disease: an investigation of 793 Chinese patients with mild and severe chronic hepatitis B and acute-on-chronic liver failure. J Gastroenterol. 2011, 46: 391-400. 10.1007/s00535-010-0315-4.CrossRefPubMed
4.
Jalan R, Williams R: Acute-on-chronic liver failure: pathophysiological basis of therapeutic options. Blood Purif. 2002, 20: 252-261. 10.1159/000047017.CrossRefPubMed
5.
Jung O, Asbe-Vollkopf A, Betz C, Caspary W, Geiger H, Faust D: Long-term therapy of acute chronic liver failure to successful transplantation with an extracorporeal liver support system. Z Gastroenterol. 2007, 45: 21-24. 10.1055/s-2006-927385.CrossRefPubMed
6.
Chen Z, Wen T, Zeng Y, Wang L, Lu JJ, Gong S, Tan H, Feng P, Li B, Zhao J, Wang W, Xu M, Yang J, Wu H, Yan L: A single institution experience with living donor liver transplantation for acute-on-chronic hepatitis b liver failure. Hepatogastroenterology. 2011, 58: 1286-1290.CrossRef
7.
Bahirwani R, Shaked O, Bewtra M, Forde K, Reddy KR: Acute-on-chronic liver failure before liver transplantation: impact on posttransplant outcomes. Transplantation. 2011, 92: 952-957. 10.1097/TP.0b013e31822e6eda.CrossRefPubMed
8.
Belkaid Y, Rouse BT: Natural regulatory T cells in infectious disease. Nat Immunol. 2005, 6: 353-360.CrossRefPubMed
9.
Peng G, Li S, Wu W, Sun Z, Chen Y, Chen Z: Circulating CD4+ CD25+ regulatory T cells correlate with chronic hepatitis B infection. Immunology. 2008, 123: 57-65. 10.1111/j.1365-2567.2007.02691.x.CrossRefPubMedPubMedCentral
10.
Nan XP, Zhang Y, Yu HT, Li Y, Sun RL, Wang JP, Bai XF: Circulating CD4 + CD25high regulatory T cells and expression of PD-1 and BTLA on CD4+ T cells in patients with chronic hepatitis B virus infection. Viral Immunol. 2010, 23: 63-70. 10.1089/vim.2009.0061.CrossRefPubMed
11.
Xu D, Fu J, Jin L, Zhang H, Zhou C, Zou Z, Zhao JM, Zhang B, Shi M, Ding X, Tang Z, Fu YX, Wang FS: Circulating and liver resident CD4 + CD25+ regulatory T cells actively influence the antiviral immune response and disease progression in patients with hepatitis B. J Immunol. 2006, 177: 739-747.CrossRefPubMed
12.
Wang LW, Chen H, Gong ZJ: High mobility group box-1 protein inhibits regulatory T cell immune activity in liver failure in patients with chronic hepatitis B. Hepatobiliary Pancreat Dis Int. 2010, 9: 499-507.PubMed
13.
Miles JJ, Douek DC, Price DA: Bias in the alphabeta T-cell repertoire: implications for disease pathogenesis and vaccination. Immunol Cell Biol. 2011, 89: 375-387. 10.1038/icb.2010.139.CrossRefPubMed
14.
Sarin SK, Kumar A, Almeida JA, Chawla YK, Fan ST, Garg H, de Silva HJ, Hamid SS, Jalan R, Komolmit P, Lau GK, Liu Q, Madan K, Mohamed R, Ning Q, Rahman S, Rastogi A, Riordan SM, Sakhuja P, Samuel D, Shah S, Sharma BC, Sharma P, Takikawa Y, Thapa BR, Wai CT, Yuen MF: Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific Association for the study of the liver (APASL). Hepatol Int. 2009, 3: 269-282. 10.1007/s12072-008-9106-x.CrossRefPubMedPubMedCentral
15.
Liver Failure and Artificial Liver Group Chinese Society of Infectious Diseases Chinese Medical Association; Severe Liver Diseases and Artificial Liver Group Chinese Society of Hepatology Chinese Medical Association: Diagnostic and treatment guidelines for liver failure. Zhonghua Gan Zang Bing Za Zhi. 2006, 14: 643-646.
16.
Wasmuth HE, Kunz D, Yagmur E, Timmer-Stranghoner A, Vidacek D, Siewert E, Bach J, Geier A, Purucker EA, Gressner AM, Matern S, Lammert F: Patients with acute on chronic liver failure display “sepsis-like” immune paralysis. J Hepatol. 2005, 42: 195-201.CrossRefPubMed
17.
Chen Y, Li X, Ye B, Yang X, Wu W, Chen B, Pan X, Cao H, Li L: Effect of telbivudine therapy on the cellular immune response in chronic hepatitis B. Antiviral Res. 2011, 91: 23-31. 10.1016/j.antiviral.2011.04.008.CrossRefPubMed
18.
Pan XB, Wei L, Han JC, Gao Y: Cellular chromosome DNA interferes with fluorescence quantitative real-time PCR detection of HBV DNA in culture medium. J Med Virol. 2008, 80: 47-52. 10.1002/jmv.21042.CrossRefPubMed
19.
Yang JZ, Li MW, Wang JG, Lu HF, Yao XS, He JQ, Li LJ: Rapid detection of clonal expansion of T-cell receptor-beta gene in patients with HBV using the real-time PCR with DNA melting curve analysis. Hepatol Res. 2010, 40: 407-414. 10.1111/j.1872-034X.2009.00600.x.CrossRefPubMed
20.
Yang J, He J, Lu H, Wei L, Li S, Wang B, Diao H, Li L: Molecular features of the complementarity determining region 3 motif of the T cell population and subsets in the blood of patients with chronic severe hepatitis B. J Transl Med. 2011, 9: 210-10.1186/1479-5876-9-210.CrossRefPubMedPubMedCentral
21.
Sing GK, Li D, Chen X, Macnaughton T, Lichanska AM, Butterworth L, Ladhams A, Cooksley G: A molecular comparison of T lymphocyte populations infiltrating the liver and circulating in the blood of patients with chronic hepatitis B: evidence for antigen-driven selection of a public complementarity-determining region 3 (CDR3) motif. Hepatology. 2001, 33: 1288-1298. 10.1053/jhep.2001.24026.CrossRefPubMed
22.
Stoop JN, van der Molen RG, Baan CC, van der Laan LJ, Kuipers EJ, Kusters JG, Janssen HL: Regulatory T cells contribute to the impaired immune response in patients with chronic hepatitis B virus infection. Hepatology. 2005, 41: 771-778. 10.1002/hep.20649.CrossRefPubMed
23.
Tsunemi S, Iwasaki T, Imado T, Higasa S, Kakishita E, Shirasaka T, Sano H: Relationship of CD4 + CD25+ regulatory T cells to immune status in HIV-infected patients. AIDS. 2005, 19: 879-886. 10.1097/01.aids.0000171401.23243.56.CrossRefPubMed
24.
Stoop JN, van der Molen RG, Kuipers EJ, Kusters JG, Janssen HL: Inhibition of viral replication reduces regulatory T cells and enhances the antiviral immune response in chronic hepatitis B. Virology. 2007, 361: 141-148. 10.1016/j.virol.2006.11.018.CrossRefPubMed
25.
Garcia-Castillo H, Barros-Nunez P: Detection of clonal immunoglobulin and T-cell receptor gene recombination in hematological malignancies: monitoring minimal residual disease. Cardiovasc Hematol Disord Drug Targets. 2009, 9: 124-135. 10.2174/187152909788488627.CrossRefPubMed
26.
Marrack P, Kappler J: Positive selection of thymocytes bearing alpha beta T cell receptors. Curr Opin Immunol. 1997, 9: 250-255. 10.1016/S0952-7915(97)80144-6.CrossRefPubMed
27.
Miqueu P, Guillet M, Degauque N, Dore JC, Soulillou JP, Brouard S: Statistical analysis of CDR3 length distributions for the assessment of T and B cell repertoire biases. Mol Immunol. 2007, 44: 1057-1064. 10.1016/j.molimm.2006.06.026.CrossRefPubMed
28.
Okajima M, Wada T, Nishida M, Yokoyama T, Nakayama Y, Hashida Y, Shibata F, Tone Y, Ishizaki A, Shimizu M, Saito T, Ohta K, Toma T, Yachie A: Analysis of T cell receptor Vbeta diversity in peripheral CD4 and CD8 T lymphocytes in patients with autoimmune thyroid diseases. Clin Exp Immunol. 2009, 155: 166-172. 10.1111/j.1365-2249.2008.03842.x.CrossRefPubMedPubMedCentral
29.
Du JW, Gu JY, Liu J, Cen XN, Zhang Y, Ou Y, Chu B, Zhu P: TCR spectratyping revealed T lymphocytes associated with graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Leuk Lymphoma. 2007, 48: 1618-1627. 10.1080/10428190701474357.CrossRefPubMed
30.
Zaccone P, Cooke A: Harnessing CD8(+) regulatory T cells: therapy for type 1 diabetes?. Immunity. 2010, 32: 504-506. 10.1016/j.immuni.2010.04.009.CrossRefPubMed
31.
Sharabi A, Mozes E: Harnessing regulatory T cells for the therapy of lupus and other autoimmune diseases. Immunotherapy. 2009, 1: 385-401. 10.2217/imt.09.2.CrossRefPubMed
32.
Davis JL, Theoret MR, Zheng Z, Lamers CH, Rosenberg SA, Morgan RA: Development of human anti-murine T-cell receptor antibodies in both responding and nonresponding patients enrolled in TCR gene therapy trials. Clin Cancer Res. 2010, 16: 5852-5861. 10.1158/1078-0432.CCR-10-1280.CrossRefPubMedPubMedCentral
33.
Kerkar SP, Sanchez-Perez L, Yang S, Borman ZA, Muranski P, Ji Y, Chinnasamy D, Kaiser AD, Hinrichs CS, Klebanoff CA, Scott CD, Gattinoni L, Morgan RA, Rosenberg SA, Restifo NP: Genetic engineering of murine CD8(+) and CD4(+) T cells for preclinical adoptive immunotherapy studies. J Immunother. 2011, 34: 343-352. 10.1097/CJI.0b013e3182187600.CrossRefPubMedPubMedCentral
34.
Bendle GM, Haanen JB, Schumacher TN: Preclinical development of T cell receptor gene therapy. Curr Opin Immunol. 2009, 21: 209-214. 10.1016/j.coi.2009.02.007.CrossRefPubMed
35.
Wang QJ, Hanada K, Feldman SA, Zhao Y, Inozume T, Yang JC: Development of a genetically-modified novel T-cell receptor for adoptive cell transfer against renal cell carcinoma. J Immunol Methods. 2011, 366: 43-51. 10.1016/j.jim.2011.01.002.CrossRefPubMedPubMedCentral
36.
Frankel TL, Burns WR, Peng PD, Yu Z, Chinnasamy D, Wargo JA, Zheng Z, Restifo NP, Rosenberg SA, Morgan RA: Both CD4 and CD8 T cells mediate equally effective in vivo tumor treatment when engineered with a highly avid TCR targeting tyrosinase. J Immunol. 2010, 184: 5988-5998. 10.4049/jimmunol.1000189.CrossRefPubMed
37.
Morgan RA, Dudley ME, Wunderlich JR, Hughes MS, Yang JC, Sherry RM, Royal RE, Topalian SL, Kammula US, Restifo NP, Zheng Z, Nahvi A, de Vries CR, Rogers-Freezer LJ, Mavroukakis SA, Rosenberg SA: Cancer regression in patients after transfer of genetically engineered lymphocytes. Science. 2006, 314: 126-129. 10.1126/science.1129003.CrossRefPubMedPubMedCentral
38.
Gehring AJ, Xue SA, Ho ZZ, Teoh D, Ruedl C, Chia A, Koh S, Lim SG, Maini MK, Stauss H, Bertoletti A: Engineering virus-specific T cells that target HBV infected hepatocytes and hepatocellular carcinoma cell lines. J Hepatol. 2011, 55: 103-110. 10.1016/j.jhep.2010.10.025.CrossRefPubMed
39.
Picarda E, Anegon I, Guillonneau C: T-cell receptor specificity of CD8(+) tregs in allotransplantation. Immunotherapy. 2011, 3: 35-37. 10.2217/imt.11.37.CrossRefPubMed
40.
Adeegbe D, Matsutani T, Yang J, Altman NH, Malek TR: CD4(+) CD25(+) Foxp3(+) T regulatory cells with limited TCR diversity in control of autoimmunity. J Immunol. 2010, 184: 56-66. 10.4049/jimmunol.0902379.CrossRefPubMedPubMedCentral
Metadata
Title
Phenotypes and clinical significance of circulating CD4+CD25+ regulatory T cells (Tregs) in patients with acute-on-chronic liver failure (ACLF)
Authors
Jiezuan Yang
Ping Yi
Li Wei
Zherong Xu
Yunbo Chen
Lingling Tang
Lanjuan Li
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2012
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/1479-5876-10-193

Other articles of this Issue 1/2012

Journal of Translational Medicine 1/2012 Go to the issue

Research

High expression of high mobility group box 1 (hmgb1) predicts poor prognosis for hepatocellular carcinoma after curative hepatectomy

Research

The Chinese medicine formula HB01 reduces choroidal neovascularization by regulating the expression of vascular endothelial growth factor

Research

Prognostic significance of MyD88 expression by human epithelial ovarian carcinoma cells

Research

Metabolomic profiling in blood from umbilical cords of low birth weight newborns

Research

Analysis of in vitro secretion profiles from adipose-derived cell populations

Research

Coculture with hematopoietic stem cells protects cardiomyocytes against apoptosis via paracrine activation of AKT
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits