Journal of Clinical Immunology

, Volume 30, Issue 1, pp 60–67

Implication of Th17 and Th1 Cells in Patients with Chronic Active Hepatitis B

  • Jian Ge
  • Kai Wang
  • Qing-Hua Meng
  • Zhao-Xia Qi
  • Fan-Li Meng
  • Yu-Chen Fan
Article

Abstract

Objective

The pathogenesis of hepatitis B virus (HBV)-associated chronic liver disease is still not fully understood. The immune imbalance of cytokine profile exerts a profound influence on the resolution of HBV infections and HBV clearance. This present study aimed to evaluate the immune status of the peripheral T helper (Th) 17 and Th1 cells in the active patients with chronic HBV infection.

Materials and Methods

Thirty patients with chronic active hepatitis B were included in our present study. The frequency of peripheral Th 17 cells (CD3+CD8IL-17+ T cells), Th1 cells (CD3+CD8IFN-γ+ T cells), and Tc1 cells (CD3+CD8+IFN-γ+ T cells) in chronic hepatitis B (CHB) were analyzed by flow cytometry. The protein and mRNA levels of interleukin-17 (IL-17) and interferon-gamma (IFN-γ) were measured by enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction (PCR).

Results

The percentage of Th17 cells in peripheral blood of CHB patients (1.53 ± 0.52%) was significantly increased than that in normal controls (0.92 ± 0.20%; P < 0.05). In contrast, the percentage of Th1 and Tc1 cells of CHB patients was significantly decreased as compared with that of control group. The frequency of Th17 cells had a negative correlation with Th1 cells, and a positive correlation with serum alanine aminotransferase in CHB patients.

Conclusion

The elevated peripheral Th17 cells were obtained in the patient with chronic active hepatitis B, suggesting its potential role in the immune activation of chronic HBV infection.

Keywords

Chronic hepatitis B T helper 17 T helper 1 

References

  1. 1.
    Lok AS. The maze of treatments for hepatitis B. N Engl J Med. 2005;352:2743–6.CrossRefPubMedGoogle Scholar
  2. 2.
    Kägi D, Ledermann B, Bürki K, Zinkernagel RM, Hengartner H. Molecular mechanisms of lymphocyte-mediated cytotoxicity and their role in immunological protection and pathogenesis in vivo. Annu Rev Immunol. 1996;14:207–32.CrossRefPubMedGoogle Scholar
  3. 3.
    Vierling JM. The immunology of hepatitis B. Clin Liver Dis. 2007;11:727–59.CrossRefPubMedGoogle Scholar
  4. 4.
    Klein J, Sato A. The HLA system. First of two parts. N Engl J Med. 2000;343:702–9.CrossRefPubMedGoogle Scholar
  5. 5.
    Klein J, Sato A. The HLA system. Second of two parts. N Engl J Med. 2000;343:782–6.CrossRefPubMedGoogle Scholar
  6. 6.
    Harrington LE, Hatton RD, Mangan PR, Turner H, Murphy TL, Murphy KM, et al. Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol. 2005;6:1123–32.CrossRefPubMedGoogle Scholar
  7. 7.
    Park H, Li Z, Yang XO, Chang SH, Nurieva R, Wang YH, et al. A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol. 2005;6:1133–41.CrossRefPubMedGoogle Scholar
  8. 8.
    Ouyang W, Kolls JK, Zheng Y. The biological functions of T helper 17 cell effector cytokines in inflammation. Immunity. 2008;28:454–67.CrossRefPubMedGoogle Scholar
  9. 9.
    Dong C. TH17 cells in development: an updated view of their molecular identity and genetic programming. Nat Rev Immunol. 2008;8:337–48.CrossRefPubMedGoogle Scholar
  10. 10.
    Ivanov II, McKenzie BS, Zhou L, Tadokoro CE, Lepelley A, Lafaille JJ, et al. The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell. 2006;126:1121–33.CrossRefPubMedGoogle Scholar
  11. 11.
    Martinez GJ, Nurieva RI, Yang XO, Dong C. Regulation and function of proinflammatory TH17 cells. Ann N Y Acad Sci. 2008;1143:188–211.CrossRefPubMedGoogle Scholar
  12. 12.
    Kolls JK, Linden A. Interleukin-17 family members and inflammation. Immunity. 2004;21:467–76.CrossRefPubMedGoogle Scholar
  13. 13.
    Langrish CL, Chen Y, Blumenschein WM, Mattson J, Basham B, Sedgwick JD, et al. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med. 2005;201:233–40.CrossRefPubMedGoogle Scholar
  14. 14.
    Ma D, Zhu X, Zhao P, Zhao C, Li X, Zhu Y, et al. Profile of Th17 cytokines (IL-17, TGF-beta, IL-6) and Th1 cytokine (IFN-gamma) in patients with immune thrombocytopenic purpura. Ann Hematol. 2008;87:899–904.CrossRefPubMedGoogle Scholar
  15. 15.
    Zhang B, Rong G, Wei H, Zhang M, Bi J, Ma L, et al. The prevalence of Th17 cells in patients with gastric cancer. Biochem Biophys Res Commun. 2008;374:533–7.CrossRefPubMedGoogle Scholar
  16. 16.
    Lemmers A, Moreno C, Gustot T, Maréchal R, Degré D, Demetter P, et al. The interleukin-17 pathway is involved in human alcoholic liver disease. Hepatology. 2009;49:646–57.CrossRefPubMedGoogle Scholar
  17. 17.
    Penna A, Del Prete G, Cavalli A, Bertoletti A, D’Elios MM, Sorrentino R, et al. Predominant T-helper 1 cytokine profile of hepatitis B virus nucleocapsid-specific T cells in acute self-limited hepatitis B. Hepatology. 1997;25:1022–7.CrossRefPubMedGoogle Scholar
  18. 18.
    Zajac AJ, Murali-Krishna K, Blattman JN, Ahmed R. Therapeutic vaccination against chronic viral infection: the importance of cooperation between CD4+ and CD8+ T cells. Curr Opin Immunol. 1998;10:444–9.CrossRefPubMedGoogle Scholar
  19. 19.
    Ferrari C, Missale G, Boni C, Urbani S. Immunopathogenesis of hepatitis B. J Hepatol. 2003;39(Suppl 1):S36–S42.CrossRefPubMedGoogle Scholar
  20. 20.
    Löhr HF, Krug S, Herr W, Weyer S, Schlaak J, Wölfel T, et al. Quantitative and functional analysis of core-specific T-helper cell and CTL activities in acute and chronic hepatitis B. Liver. 1998;18:405–13.PubMedGoogle Scholar
  21. 21.
    Kondo Y, Kobayashi K, Ueno Y, Shiina M, Niitsuma H, Kanno N, et al. Mechanism of T cell hyporesponsiveness to HBcAg is associated with regulatory T cells in chronic hepatitis B. World J Gastroenterol. 2006;12:4310–7.PubMedGoogle Scholar
  22. 22.
    Akpolat N, Yahsi S, Godekmerdan A, Demirbag K, Yalniz M. Relationship between serum cytokine levels and histopathological changes of liver in patients with hepatitis B. World J Gastroenterol. 2005;11:3260–3.PubMedGoogle Scholar
  23. 23.
    Jiang R, Feng X, Guo Y, Lu Q, Hou J, Luo K, et al. T helper cells in patients with chronic hepatitis B virus infection. Chin Med J (Engl). 2002;115:422–4.Google Scholar
  24. 24.
    Bettelli E, Oukka M, Kuchroo VK. T(H)-17 cells in the circle of immunity and autoimmunity. Nat Immunol. 2007;8:345–50.CrossRefPubMedGoogle Scholar
  25. 25.
    Shahrara S, Huang Q, Mandelin AM 2nd, Pope RM. TH-17 cells in rheumatoid arthritis. Arthritis Res Ther. 2008;10:R93.CrossRefPubMedGoogle Scholar
  26. 26.
    Prussin C. Cytokine flow cytometry: understanding cytokine biology at the single-cell level. J Clin Immunol. 1997;17:195–204.CrossRefPubMedGoogle Scholar
  27. 27.
    Pène J, Chevalier S, Preisser L, Vénéreau E, Guilleux MH, Ghannam S, et al. Chronically inflamed human tissues are infiltrated by highly differentiated Th17 lymphocytes. J Immunol. 2008;180:7423–30.PubMedGoogle Scholar
  28. 28.
    Luger D, Silver PB, Tang J, Cua D, Chen Z, Iwakura Y, et al. Either a Th17 or a Th1 effector response can drive autoimmunity: conditions of disease induction affect dominant effector category. J Exp Med. 2008;205:799–810.CrossRefPubMedGoogle Scholar
  29. 29.
    Bertoletti A, Costanzo A, Chisari FV, Levrero M, Artini M, Sette A, et al. Cytotoxic T lymphocyte response to a wild type hepatitis B virus epitope in patients chronically infected by variant viruses carrying substitutions within the epitope. J Exp Med. 1994;180:933–43.CrossRefPubMedGoogle Scholar
  30. 30.
    Yan MX, Mao HT, Liu Q, Wang WQ, Li YQ. Elevated levels of serum soluble E-selectin in patients with chronic hepatitis B: correlation with T lymphocyte subsets, NK cells and liver inflammation. Hepatol Res. 2006;35:111–7.CrossRefPubMedGoogle Scholar
  31. 31.
    Tang TJ, Kwekkeboom J, Laman JD, Niesters HG, Zondervan PE, de Man RA, et al. The role of intrahepatic immune effector cells in inflammatory liver injury and viral control during chronic hepatitis B infection. J Viral Hepat. 2003;10:159–67.CrossRefPubMedGoogle Scholar
  32. 32.
    Kim WR, Flamm SL, Di Bisceglie AM, Bodenheimer HC. Serum activity of alanine aminotransferase (ALT) as an indicator of health and disease. Hepatology. 2008;47:1363–70.CrossRefPubMedGoogle Scholar
  33. 33.
    Xu Y, Du WJ, Qin LY, Xing ZZ, Qin XH, Chen SJ. Expression of interleukin-17 in hepatitis B related liver fibrosis. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2009;25:133–5.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Jian Ge
    • 1
  • Kai Wang
    • 1
  • Qing-Hua Meng
    • 2
  • Zhao-Xia Qi
    • 1
  • Fan-Li Meng
    • 1
  • Yu-Chen Fan
    • 1
  1. 1.Department of Hepatology, Qilu HospitalShandong UniversityJinanChina
  2. 2.Department of Hepatology, Beijing YouAn HospitalCapital Medical UniversityBeijingChina

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