Up-regulation of FOXP3 and induction of suppressive function in CD4 + Jurkat T-cells expressing hepatitis C virus core protein

Clinical Science

Volumn 123, Issue 1, 2012, Pages 15-27

  Dominguez Villar, Margarita ^a   Fernandez Ponce, Cecilia ^a   Munoz Suano, Alba ^a   Gomez, Esperanza ^a   Rodríguez Iglesias, Manuel ^a   Garcia Cozar, Francisco ^a  

^a HOSPITAL UNIVERSITARIO DE PUERTO REAL   (Spain)

Author keywords

CD4; Forkhead box P3 (FOXOP3); Hepatitis C virus; Immune evasion; Immune tolerance; Regulatory T cell

Indexed keywords

CD28 ANTIGEN; CD3 ANTIGEN; COMPLEMENTARY DNA; CORE PROTEIN; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; INTERLEUKIN 2; LENTIVIRUS VECTOR; MESSENGER RNA; NUCLEAR PROTEIN; PLASMID VECTOR; TRANSCRIPTION FACTOR FOXP3; FORKHEAD TRANSCRIPTION FACTOR; FOXP3 PROTEIN, HUMAN; HEPATITIS C ANTIGEN; IL2RA PROTEIN, HUMAN; INTERLEUKIN 2 RECEPTOR ALPHA;

ANTIGEN EXPRESSION; APOPTOSIS; ARTICLE; CD25+ T LYMPHOCYTE; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELL PROLIFERATION; CELL STRAIN HEK293; DNA SYNTHESIS; ENZYME INDUCTION; GENETIC TRANSDUCTION; HEPATITIS C; HUMAN; HUMAN CELL; HUMAN CELL CULTURE; IMMUNE RESPONSE; IMMUNOLOGICAL TOLERANCE; LEUKEMIA CELL LINE; PERIPHERAL BLOOD MONONUCLEAR CELL; PRIORITY JOURNAL; REAL TIME POLYMERASE CHAIN REACTION; REGULATORY T LYMPHOCYTE; RNA PURIFICATION; VIRAL CLEARANCE; CELLULAR IMMUNITY; HEPATITIS C VIRUS; IMMUNOLOGY; METABOLISM; POLYACRYLAMIDE GEL ELECTROPHORESIS; UPREGULATION; VIROLOGY; WESTERN BLOTTING;

BLOTTING, WESTERN; CD8-POSITIVE T-LYMPHOCYTES; CTLA-4 ANTIGEN; ELECTROPHORESIS, POLYACRYLAMIDE GEL; FORKHEAD TRANSCRIPTION FACTORS; HEPACIVIRUS; HEPATITIS C ANTIGENS; HEPATITIS C, CHRONIC; HUMANS; IMMUNITY, CELLULAR; INTERLEUKIN-2; INTERLEUKIN-2 RECEPTOR ALPHA SUBUNIT; JURKAT CELLS; REAL-TIME POLYMERASE CHAIN REACTION; T-LYMPHOCYTES, REGULATORY; TRANSDUCTION, GENETIC; UP-REGULATION; VIRAL CORE PROTEINS;

EID: 84860227446     PISSN: 01435221     EISSN: None     Source Type: Journal    
DOI: 10.1042/CS20110631     Document Type: Article

References (80)

1. Dehesa-Violante, M. and Nunez-Nateras, R. (2007) Epidemiology of hepatitis virus B and C. Arch. Med. Res. 38, 606-611.
2. Moradpour, D., Penin, F. and Rice, C. M. (2007) Replication of hepatitis C virus. Nat. Rev. Microbiol. 5, 453-463.
3. Matsumori, A., Yutani, C., Ikeda, Y., Kawai, S. and Sasayama, S. (2000) Hepatitis C virus from the hearts of patients with myocarditis and cardiomyopathy. Lab. Invest. 80, 1137-1142.
4. Kondo, Y., Sung, V. M. H., Machida, K., Liu, M. and Lai, M. M. C. (2007) Hepatitis C virus infects T cells and affects interferon-γ signaling in T cell lines. Virology 361, 161-173.
5. Castillo, I., Rodriguez-Inigo, E., Bartolome, J., de Lucas, S., Ortiz-Movilla, N., Lopez-Alcorocho, J. M., Pardo, M. and Carreno, V. (2005) Hepatitis C virus replicates in peripheral blood mononuclear cells of patients with occult hepatitis C virus infection. Gut 54, 682-685.
6. Blackard, J. T., Smeaton, L., Hiasa, Y., Horiike, N., Onji, M., Jamieson, D. J., Rodriguez, I., Mayer, K. H. and Chung, R. T. (2005) Detection of hepatitis C virus (HCV) in serum and peripheral-blood mononuclear cells from HCV-monoinfected and HIV/HCV-coinfected persons. J. Infect. Dis. 192, 258-265.
7. Laskus, T., Operskalski, E. A., Radkowski, M., Wilkinson, J., Mack, W. J., deGiacomo, M., Al-Harthi, L., Chen, Z., Xu, J. and Kovacs, A. (2007) Negative-strand hepatitis C virus (HCV) RNA in peripheral blood mononuclear cells from anti-HCV-positive/HIV-infected women. J. Infect. Dis. 195, 124-133.
8. El-Awady, M. K., Tabll, A. A., Redwan El, R. M., Youssef, S., Omran, M. H., Thakeb, F. and El-Demellawy, M. (2005) Flow cytometric detection of hepatitis C virus antigens in infected peripheral blood leukocytes: binding and entry. World J. Gastroenterol. 11, 5203-5208.
9. Pal, S., Sullivan, D. G., Kim, S., Lai, K. K., Kae, J., Cotler, S. J., Carithers, Jr, R. L.,Wood, B. L., Perkins, J. D. and Gretch, D. R. (2006) Productive replication of hepatitis C virus in perihepatic lymph nodes in vivo: implications of HCV lymphotropism. Gastroenterology 130, 1107-1116.
10. Laskus, T., Radkowski, M., Wang, L. F., Vargas, H. and Rakela, J. (1998) The presence of active hepatitis C virus replication in lymphoid tissue in patients coinfected with human immunodeficiency virus type 1. J. Infect. Dis. 178, 1189-1192.
11. Dominguez-Villar, M., Munoz-Suano, A., Anaya-Baz, B., Aguilar, S., Novalbos, J. P., Giron, J. A., Rodriguez-Iglesias, M. and Garcia-Cozar, F. (2007) Hepatitis C virus core protein up-regulates anergy-related genes and a new set of genes, which affects T cell homeostasis. J. Leukocyte Biol. 82, 1301-1310.
12. Shoukry, N. H., Cawthon, A. G. and Walker, C. M. (2004) Cell-mediated immunity and the outcome of hepatitis C virus infection. Annu. Rev. Microbiol. 58, 391-424.
13. Koziel, M. J. (2005) Cellular immune responses against hepatitis C virus. Clin. Infect. Dis. 41 (Suppl. 1), S25-S31.
14. Neumann-Haefelin, C., Blum, H. E., Chisari, F. V. and Thimme, R. (2005) T cell response in hepatitis C virus infection. J. Clin. Virol. 32, 75-85.
15. Bowen, D. G. and Walker, C. M. (2005) Adaptive immune responses in acute and chronic hepatitis C virus infection. Nature 436, 946-952.
16. Thimme, R., Oldach, D., Chang, K. M., Steiger, C., Ray, S. C. and Chisari, F. V. (2001) Determinants of viral clearance and persistence during acute hepatitis C virus infection. J. Exp. Med. 194, 1395-1406.
17. + T-helper-cell responses in resolved hepatitis C virus infection. J. Virol. 76, 12584-12595.
18. + T lymphocytes after infection with hepatitis C virus. J. Virol. 75, 5550-5558.
19. Ulsenheimer, A., Gerlach, J. T., Gruener, N. H., Jung, M. C., Schirren, C. A., Schraut, W., Zachoval, R., Pape, G. R. and Diepolder, H. M. (2003) Detection of functionally altered hepatitis C virus-specific CD4 T cells in acute and chronic hepatitis C. Hepatology 37, 1189-1198.
20. Day, C. L. and Walker, B. D. (2003) Progress in defining CD4 helper cell responses in chronic viral infections. J. Exp. Med. 198, 1773-1777.
21. + T cells in chronic hepatitis C virus infection. J. Immunol. 169, 3447-3458.
22. Thimme, R., Bukh, J., Spangenberg, H. C., Wieland, S., Pemberton, J., Steiger, C., Govindarajan, S., Purcell, R. H. and Chisari, F. V. (2002) Viral and immunological determinants of hepatitis C virus clearance, persistence, and disease. Proc. Natl. Acad. Sci. U.S.A. 99, 15661-15668.
23. + T helper cells in chronic HCV infection. Hepatology 41, 1019-1028.
24. Sundstrom, S., Ota, S., Dimberg, L. Y., Masucci, M. G. and Bergqvist, A. (2005) Hepatitis C virus core protein induces an anergic state characterized by decreased interleukin-2 production and perturbation of mitogen-activated protein kinase responses. J. Virol. 79, 2230-2239.
25. Billerbeck, E., Bottler, T. and Thimme, R. (2007) Regulatory T cells in viral hepatitis. World J. Gastroenterol. 13, 4858-4864.
26. + regulatory T lymphocytes in hepatitis C virus infection. Hepatology 40, 1062-1071.
27. Sugimoto, K., Ikeda, F., Stadanlick, J., Nunes, F. A., Alter, H. J. and Chang, K. M. (2003) Suppression of HCV-specific T cells without differential hierarchy demonstrated ex vivo in persistent HCV infection. Hepatology 38, 1437-1448.
28. + IFN-γ - regulatory T cells in chronic hepatitis C virus infection. Immunol. Cell. Biol. 85, 197-204.
29. Li, S., Gowans, E. J., Chougnet, C., Plebanski, M. and Dittmer, U. (2007) Natural regulatory T cells and persistent viral infection. J. Virol. 82, 21-30.
30. + T cell response in HCV-infected patients with normal versus abnormal alanine aminotransferase levels. Clin. Exp. Immunol. 144, 188-196.
31. + T cells during persistent hepatitis C virus infection. J. Virol. 79, 7852-7859.
32. + T lymphocytes and relation to hepatic inflammation during chronic HCV infection. J. Hepatol. 47, 316-324.
33. Bluestone, J. A. and Abbas, A. K. (2003) Natural versus adaptive regulatory T cells. Nat. Rev. Immunol. 3, 253-257.
34. Miyara, M. and Sakaguchi, S. (2007) Natural regulatory T cells: mechanisms of suppression. Trends. Mol. Med. 13, 108-116.
35. + regulatory cells that control intestinal inflammation. J. Exp. Med. 192, 295-302.
36. + regulatory T cells through GITR breaks immunological self-tolerance. Nat. Immunol. 3, 135-142.
37. Curiel, T. J. (2007) Regulatory T-cell development: is FoxP3 the decider? Nat. Med. 13, 250-253.
38. Zheng, Y. and Rudensky, A. Y. (2007) FoxP3 in control of the regulatory T cell lineage. Nat. Immunol. 8, 457-462.
39. Campbell, D. J. and Ziegler, S. F. (2007) FOXP3 modifies the phenotypic and functional properties of regulatory T cells. Nat. Rev. Immunol. 7, 305-310.
40. Shevach, E. M. (2006) From vanilla to 28 flavors: multiple varieties of T regulatory cells. Immunity 25, 195-201.
41. + T cells in the periphery. Nat. Rev. Immunol. 7, 231-237.
42. + T cells during chronic hepatitis C virus infection. J. Virol. 79, 7860-7867.
43. Chen, T.-C., Cobbold, S. P., Fairchild, P. J. and Waldmann, H. (2004) Generation of anergic and regulatory T cells following prolonged exposure to a harmless antigen. J. Immunol. 172, 5900-5907.
44. + CD4 T cells in vivo after induction of peripheral tolerance with intravenous or oral antigen. J. Immunol. 167, 188-195.
45. Knoechel, B., Lohr, J., Zhu, S., Wong, L., Hu, D., Ausubel, L. and Abbas, A. K. (2006) Functional and Molecular Comparison of Anergic and Regulatory T Lymphocytes. J. Immunol. 176, 6473-6483.
46. + regulatory T-cell lines from human cord blood have functional and molecular properties of T-cell anergy. Blood 106, 3068-3073.
47. Baan, C. C., van derMast, B. J.,Klepper,M., Mol, W. M., Peeters, A. M., Korevaar, S. S., Balk, A. H. and Weimar, W. (2005) Differential effect of calcineurin inhibitors, anti-CD25 antibodies and rapamycin on the induction of FOXP3 in human T cells. Transplantation 80, 110-117.
48. + T regulatory cells in humans. Hum. Immunol. 66, 13-20.
49. + T cells. Eur. J. Immunol. 37, 129-138.
50. + regulatory T-cell function by calcineurin-dependent interleukin-2 production. Blood 108, 390-399.
51. Kim, J.-Y., Kim, H.-J., Hurt, E. M., Chen, X., Howard, O. M. Z. and Farrar, W. L. (2007) Functional and genomic analyses of FOXP3-transduced Jurkat-T cells as regulatory T (Treg)-like cells. Biochem. Biophys. Res. Commun. 362, 44-50.
52. Wu, Y., Borde, M., Heissmeyer, V., Feuerer, M., Lapan, A. D., Stroud, J. C., Bates, D. L., Guo, L., Han, A., Ziegler, S. F. et al. (2006) FOXP3 controls regulatory T cell function through cooperation with NFAT. Cell 126, 375-387.
53. Mantel, P. Y., Ouaked, N., Ruckert, B., Karagiannidis, C., Welz, R., Blaser, K. and Schmidt-Weber, C. B. (2006) Molecular mechanisms underlying FOXP3 induction in human T cells. J. Immunol. 176, 3593-3602.
54. Fontenot, J. D., Rasmussen, J. P., Williams, L. M., Dooley, J. L., Farr, A. G. and Rudensky, A. Y. (2005) Regulatory T cell lineage specification by the forkhead transcription factor FoxP3. Immunity 22, 329-341.
55. Gibson, H. M., Hedgcock, C. J., Aufiero, B. M.,Wilson, A. J., Hafner, M. S., Tsokos, G. C. and Wong, H. K. (2007) Induction of the CTLA-4 gene in human lymphocytes is dependent on NFAT binding the proximal promoter. J. Immunol. 179, 3831-3840.
56. Macian, F. (2005) NFAT proteins: key regulators of T-cell development and function. Nat. Rev. Immunol. 5, 472-484.
57. Macian, F., Im, S. H., Garcia-Cozar, F. J. and Rao, A. (2004) T-cell anergy. Curr. Opin. Immunol. 16, 209-216.
58. Borde, M., Barrington, R. A., Heissmeyer, V., Carroll, M. C. and Rao, A. (2006) Transcriptional basis of lymphocyte tolerance. Immunol. Rev. 210, 105-119.
59. + T cells is linked to antigen recognition and T cell differentiation. PLoS Pathog. 6, e1000947.
60. + T cells defines a distinct functional subset with tissue-homing properties. Proc. Natl. Acad. Sci. U.S.A. 107, 3006-3011.
61. + T cells vary in differentiation phenotype in different persistent virus infections. Nat. Med. 8, 379-385.
62. Lee, J., Suh, W. I. and Shin, E. C. (2010) T-cell dysfunction and inhibitory receptors in hepatitis C virus infection. Immune Netw. 10, 120-125.
63. + regulatory T cells in hepatitis C virus infection. J. Virol. 82, 5043-5053.
64. Nakamoto, N., Cho, H., Shaked, A., Olthoff, K., Valiga, M. E., Kaminski, M., Gostick, E., Price, D. A., Freeman, G. J.,Wherry, E. J. and Chang, K. M. (2009) Synergistic reversal of intrahepatic HCV-specific CD8 T cell exhaustion by combined PD-1/CTLA-4 blockade. PLoS Pathog. 5, e1000313.
65. Nakamoto, N., Kaplan, D. E., Coleclough, J., Li, Y., Kaminski, M., Shaked, A., Olthoff, K., Gostick, E., Price, D. A., Freeman, G. J. et al. (2008) Functional restoration of HCV-specific CD8 T-cells by PD1 blockade is defined by PD1 expression and compartmentalization. Gastroenterology. 134, 1927-1937.
66. Manigold, T. and Racanelli, V. (2007) T-cell regulation by CD4 regulatory T cells during hepatitis B and C virus infections: facts and controversies. Lancet Infect. Dis. 7, 804-813.
67. Racanelli, V., Leone, P. and Grakoui, A. (2011) A spatial view of the CD8(+) T-cell response: the case of HCV. Rev. Med. Virol. 21, 347-357.
68. Castello, G., Scala, S., Palmieri, G., Curley, S. A. and Izzo, F. (2010) HCV-related hepatocellular carcinoma: from chronic inflammation to cancer. Clin. Immunol. 134, 237-250.
69. Reference deleted.
70. Rehermann, B. (2009) Hepatitis C virus versus innate and adaptive immune responses: a tale of coevolution and coexistence. J. Clin. Invest. 119, 1745-1754.
71. Sturm, N., Thelu, M. A., Camous, X., Dimitrov, G., Ramzan, M., Dufeu-Duchesne, T., Bonorino, P., Guillermet, C., Brambilla, E., Arvers, P. et al. (2010) Characterization and role of intra-hepatic regulatory T cells in chronic hepatitis C pathogenesis. J. Hepatol. 53, 25-35.
72. Safadi, R., Ohta, M., Alvarez, C. E., Fiel, M. I., Bansal, M., Mehal, W. Z. and Friedman, S. L. (2004) Immune stimulation of hepatic fibrogenesis by CD8 cells and attenuation by transgenic interleukin-10 from hepatocytes. Gastroenterology 127, 870-882.
73. Muhanna, N., Doron, S., Wald, O., Horani, A., Eid, A., Pappo, O., Friedman, S. L. and Safadi, R. (2008) Activation of hepatic stellate cells after phagocytosis of lymphocytes: a novel pathway of fibrogenesis. Hepatology 48, 963-977.
74. Klenerman, P. and Thimme, R. (2011) T cell responses in hepatitis C: the good, the bad and the unconventional. Gut, doi: 10.1136/gutjnl-2011-300620.
75. Yoshida, K., Ohishi, W., Nakashima, E., Fujiwara, S., Akahoshi, M., Kasagi, F., Chayama, K., Hakoda, M., Kyoizumi, S., Nakachi, K. et al. (2011) Lymphocyte subset characterization associated with persistent hepatitis C virus infection and subsequent progression of liver fibrosis. Hum. Immunol. 72, 821-826.
76. Kornek, M., Popov, Y., Libermann, T. A., Afdhal, N. H. and Schuppan, D. (2011) Human T cell microparticles circulate in blood of hepatitis patients and induce fibrolytic activation of hepatic stellate cells. Hepatology 53, 230-242.
77. Yao, Z. Q., Eisen-Vandervelde, A., Ray, S. and Hahn, Y. S. (2003) HCV core/gC1qR interaction arrests T cell cycle progression through stabilization of the cell cycle inhibitor p27Kip1. Virology 314, 271-282.
78. Falcon, V., Acosta-Rivero, N., Shibayama, M., Chinea, G., Gavilondo, J. V., de la Rosa, M. C., Menendez, I., Gra, B., Duenas-Carrera, S., Vina, A. et al. (2005) HCV core protein localizes in the nuclei of nonparenchymal liver cells from chronically HCV-infected patients. Biochem. Biophys. Res. Commun. 329, 1320-1328.
79. Maillard, P., Krawczynski, K., Nitkiewicz, J., Bronnert, C., Sidorkiewicz, M., Gounon, P., Dubuisson, J., Faure, G., Crainic, R. and Budkowska, A. (2001) Nonenveloped nucleocapsids of hepatitis C virus in the serum of infected patients. J. Virol. 75, 8240-8250.
80. Tsitoura, P., Georgopoulou, U., Petres, S., Varaklioti, A., Karafoulidou, A., Vagena, D., Politis, C. and Mavromara, P. (2007) Evidence for cellular uptake of recombinant hepatitis C virus non-enveloped capsid-like particles. FEBS Lett. 581, 4049-4057.