APPROPRIATE INDUCTION OF T REGULATORY CELLS AND HBV TOLERANCE: IMPLICATIONS FOR IMMUNOTHERAPY OF AUTOIMMUNE DISEASES
Abstract
Opposed to autoimmune diseases the immune tolerance to hepatitis B virus (HBV) has been related to inadequate HBV-specific immune response in addition to the high frequency and over expression of CD4+CD25+ T regulatory cells (Treg); however the exact mechanisms behind the induction of Treg cells in HBV infection are yet to be addressed. Generally Treg cells consist of diverse lymphocyte populations that include CD4+ cells, CD8+ cells, and other minor T cell populations. Several different mechanisms have been evolved to inhibit different immune responses, while many studies imply a cytokine-independent suppressive role of Treg cells in vitro, however accumulating evidence suggest the in vivo immunosuppressive activity of these cells against infection as well as autoimmunity needs cytokines. It is well documented that HBV Dane particles play a vital role in the immunopathogenesis of HBV infection and it has been associated with increased Treg cells which express various memory or activation markers. Based on that, alternative or indirect way of inducing Treg cells which could be a useful tool to ameliorate and/or treat autoimmune diseases is the top research priority. In this review we attempt to emphasize the role of HBV Dane particles (virions) on the induction of Treg cells and immune tolerance in HBV and we also discuss the relevance to search for new immunotherapeutic targets for autoimmune diseases.
References
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29. Shevach EM. (2002). CD4+CD25+ suppressor T cells: more questions than answers. Nat Rev Immunol; 2:389–400.
30. Groux H, O’Garra A, Bigle M, Rouleau M, Antonenko S, de Vries JE, et al (1997). A CD4+ T cell subset inhibits antigen specific T cell responses and prevents colitis. Nature; 389:737–42.
31. Levings MK, Roncarolo MG. (2000) T regulatory cells: a novel subset of CD4 T cells with immunoregulatory properties. J Allergy Clin Immunol; 106:S109-12.
32. Weiner HL. (2001). Induction and mechanism of action of transforming growth factor-beta-secreting Th3 regulatory cells. Immunol Rev; 182:207–14.
33. Yamagiwa S, Gray JD, Hashimoto S, Horwitz DA. (2001). A role for TGF-beta in the generation and expansion of CD4+CD25+ regulatory T cells from human peripheral blood. J Immunol; 166:7282–9.
2. Zhang JY, Song CH, Shi F, Zhang Z, Fu JL, Wang FS. (2010). Decreased ratio of Treg cells to Th17 cells correlates with HBV DNA suppression in chronic hepatitis B patients undergoing entecavir treatment. PLoS One; 5(11):13869-15.
3. Peter Karayiannis (2003). Hepatitis B virus: old, new and future approaches to antiviral treatment. Journal of Antimicrobial Chemotherapy; 51, 761–785.
4. Kriegel MA et al. (2004). Defective suppressor function of human CD4+CD25+ regulatory T cells in autoimmune polyglandular syndrome type II. J Exp Med; 199(9): 1285–91.
5. Roncarolo MG, Bacchetta R, Bordignon C, Narula S, Levings MK, et al. (2001) Type 1 T regulatory cells. Immunol Rev; 182: 68–79.
6. Hoffmann P, Boeld TJ, Eder R, Albrecht J, Doser K, Piseshka B, Dada A, Niemand C, Assenmacher M, Orso E, Andreesen R, Holler E, Edinger M. (2006). Isolation of CD4+CD25+ regulatory T cells for clinical trials. Biol Blood Marrow Transplant; 12(3):267-74.
7. David A. Horwitz, Song Guo Zheng, J. Dixon Gray, Ju Hua Wang, Kazuo Ohtsuka, Satoshi Yamagiwa. (2004). Regulatory T cells generated ex vivo as an approach for the therapy of autoimmune disease. Seminars in Immunology; 16 135–143
8. Sakaguchi, S., N. Sakaguchi, M. Asano, M. Itoh, and M. Toda. (1995). 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. Immunol; 155:1151–1164.
9. Baecher-Allan C, Hafler DA. (2004). Suppressor T cells in human diseases. J Exp Med; 200(3):273–6.
10. Stoop JN, van der Molen RG, Baan CC, van der Laan LJW, Kuipers EJ, Kusters JG, et al. (2005). Regulatory T cells contribute to the impaired immune response in patients with chronic hepatitis B virus infection. Hepatology; 41:771-778.
11. Franzese O, Kennedy PT, Gehring AJ, Gotto J, Williams R, Maini MK, Bertoletti A. (2005). Modulation of the CD8 T cell response by CD4+CD25+ regulatory T cells in patients with hepatitis B virus infection. J Virol; 79:3322-3328.
12. Cabrera R, Tu Z, Xu Y, Firpi RJ, Rosen HR, Liu C, et al. (2004). An immunomodulatory role for CD4+CD25+ regulatory T lymphocytes in hepatitis C virus infection. Hepatology; 40:1062-1071.
13. Tobias Boettler, Hans Christian Spangenberg, Christoph Neumann-Haefelin, Elisabeth Panther, Simonetta Urbani, Carlo Ferrari, Hubert E. Blum, Fritz von Weizsäcker, and Robert Thimme. (2005). T Cells with a CD4+CD25+ regulatory phenotype suppress in vitro proliferation of virus specific CD8+ T cells during chronic hepatitis C virus infection. J Virol; 79 (12): 7860–7867.
14. Barboza L, Salmen S, Goncalves L, Colmenares M, Peterson D, Montes H, Cartagirone R, Gutiérrez Mdel C, Berrueta L. (2007). Antigen-induced regulatory T cells in HBV chronically infected patients. Virology;368(1):41-9.
15. Gao LF, Sun WS, Ma CH, Liu SX, Wang XY, Zhang LN, Cao YL, Zhu FL, Liu YG (2004) Establishment of mice model with human viral hepatitis B. World J Gastroenterol;10(6):841-846.
16. Bai GQ, Liu Y, Cheng J, Zhang SL, Yue YF, Huang YP, Zhang LY. (2005) Trans-activating effect of complete S protein of hepatitis B virus and cloning of genes trans-activated by complete S protein using suppression subtractive hybridization technique. World J Gastroenterol; 11(25):3893-3898.
17. Musacchio A, Ernesto G. Rodriguez, Antonieta M. Herrera, Diogenes Quintana, and Verena Muzio. (2001) Multivalent DNA-Based immunization against Hepatitis B Virus with plasmids encoding surface and core antigens. Biochemical and Biophysical Research Communications; 282: 442–446.
18. Riedl P, Stober D, Oehninger C, Melber K, Reimann J, and Schirmbeck R. (2002). Priming Th1 immunity to viral core particles is facilitated by trace amounts of RNA bound to its Arginine-Rich domain. The Journal of Immunology; 168: 4951–4959.
19. Bulut Y, Bulut H, Doymaz MZ. (2003.) Immunization of mice with plasmid DNA encoding Hepatitis B Virus core antigen (HBcAg). Turk J Med Sci; 33 61-63.
20. Zhang SJ, Chen HY, Chen ZX, Wang XZ. (2005). Possible mechanism for hepatitis B virus X gene to induce apoptosis of hepatocytes. World J Gastroenterol; 11(28):4351-4356.
21. Schäfer, S., Tolle, T., Lottmann, S. & Gerlich, W. H. (1998). Animal models and experimental systems in hepatitis B virus research. In Hepatitis B Virus: Molecular Mechanisms in Disease and Novel Strategies for Therapy (Koshy, R. C. & Caselmann, W. H., Eds), pp. 51–74.
22. Stuyver L, De Gendt S, Van Geyt C, et al. (2000). A new genotype of hepatitis B virus: complete genome and phylogenetic relatedness. J Gen Virol; 81:67–74
23. Ganem, D. and R. J. Schneider. (2001). Hepadnaviridae and their replication p. 2923–2970. In D. M. Knipe, P. M. Howley, D. E. Griffin, R. A. Lamb, B. Roizman, M. A. Martin, and S. E. Straus (ed.), Fields virology, 4th ed. Lippincott Raven Publishers, Philadelphia, Pa.
24. Seeger, C. & Mason, W. S. (2000). Hepatitis B virus biology. Imperial College Press, London, UK. Microbiology and Molecular Biology Reviews, 64, 51–68.
25. Ehrenstein MR, et al. (2004) Compromised function of regulatory T cells in rheumatoid arthritis and reversal by anti TNF alpha therapy. J Exp Med; 200(3):277–85.
26. Xuanyong Lu, Timothy Block. (2004). Study of the early steps of the Hepatitis B Virus life cycle. Int. J. Med. Sci. 1(1): 21-33.
27. Wing K, Suri-Payery E & Rudin A. (2005). CD4+CD25+ Regulatory T Cells from Mouse to Man. Scandanavian Journal of Immunology; 62; 1–15.
28. McHugh RS, Shevach EM. (2002). The role of suppressor T cells in regulation of immune responses. J Allergy Clin Immunol; 110:693–702.
29. Shevach EM. (2002). CD4+CD25+ suppressor T cells: more questions than answers. Nat Rev Immunol; 2:389–400.
30. Groux H, O’Garra A, Bigle M, Rouleau M, Antonenko S, de Vries JE, et al (1997). A CD4+ T cell subset inhibits antigen specific T cell responses and prevents colitis. Nature; 389:737–42.
31. Levings MK, Roncarolo MG. (2000) T regulatory cells: a novel subset of CD4 T cells with immunoregulatory properties. J Allergy Clin Immunol; 106:S109-12.
32. Weiner HL. (2001). Induction and mechanism of action of transforming growth factor-beta-secreting Th3 regulatory cells. Immunol Rev; 182:207–14.
33. Yamagiwa S, Gray JD, Hashimoto S, Horwitz DA. (2001). A role for TGF-beta in the generation and expansion of CD4+CD25+ regulatory T cells from human peripheral blood. J Immunol; 166:7282–9.
Published
2011-06-01
How to Cite
ELTAHIR KHALID, Khalid et al.
APPROPRIATE INDUCTION OF T REGULATORY CELLS AND HBV TOLERANCE: IMPLICATIONS FOR IMMUNOTHERAPY OF AUTOIMMUNE DISEASES.
Gezira Journal of Health Sciences, [S.l.], v. 7, n. 1, june 2011.
ISSN 1810-5386. Available at: <http://37.60.236.48/index.php/gjhs/article/view/282>. Date accessed: 03 june 2026.
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