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

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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+CD8−IL-17+ T cells), Th1 cells (CD3+CD8−IFN-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.

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References

  1. Lok AS. The maze of treatments for hepatitis B. N Engl J Med. 2005;352:2743–6.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  3. Vierling JM. The immunology of hepatitis B. Clin Liver Dis. 2007;11:727–59.

    Article  PubMed  Google Scholar 

  4. Klein J, Sato A. The HLA system. First of two parts. N Engl J Med. 2000;343:702–9.

    Article  PubMed  CAS  Google Scholar 

  5. Klein J, Sato A. The HLA system. Second of two parts. N Engl J Med. 2000;343:782–6.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  8. Ouyang W, Kolls JK, Zheng Y. The biological functions of T helper 17 cell effector cytokines in inflammation. Immunity. 2008;28:454–67.

    Article  PubMed  CAS  Google Scholar 

  9. Dong C. TH17 cells in development: an updated view of their molecular identity and genetic programming. Nat Rev Immunol. 2008;8:337–48.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  12. Kolls JK, Linden A. Interleukin-17 family members and inflammation. Immunity. 2004;21:467–76.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  19. Ferrari C, Missale G, Boni C, Urbani S. Immunopathogenesis of hepatitis B. J Hepatol. 2003;39(Suppl 1):S36–S42.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    CAS  Google Scholar 

  24. Bettelli E, Oukka M, Kuchroo VK. T(H)-17 cells in the circle of immunity and autoimmunity. Nat Immunol. 2007;8:345–50.

    Article  PubMed  CAS  Google Scholar 

  25. Shahrara S, Huang Q, Mandelin AM 2nd, Pope RM. TH-17 cells in rheumatoid arthritis. Arthritis Res Ther. 2008;10:R93.

    Article  PubMed  CAS  Google Scholar 

  26. Prussin C. Cytokine flow cytometry: understanding cytokine biology at the single-cell level. J Clin Immunol. 1997;17:195–204.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by grants from Key Project of Chinese Ministry of Science and Technology (2008ZX10002-007).

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Authors and Affiliations

  1. Department of Hepatology, Qilu Hospital, Shandong University, 107 West Wenhua Rd, Jinan, 250012, China

    Jian Ge, Kai Wang, Zhao-Xia Qi, Fan-Li Meng & Yu-Chen Fan

  2. Department of Hepatology, Beijing YouAn Hospital, Capital Medical University, Beijing, 100069, China

    Qing-Hua Meng

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  1. Jian Ge
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  2. Kai Wang
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  3. Qing-Hua Meng
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  4. Zhao-Xia Qi
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Correspondence to Kai Wang.

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Ge, J., Wang, K., Meng, QH. et al. Implication of Th17 and Th1 Cells in Patients with Chronic Active Hepatitis B. J Clin Immunol 30, 60–67 (2010). https://doi.org/10.1007/s10875-009-9328-2

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  • DOI: https://doi.org/10.1007/s10875-009-9328-2

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