CD4+ T cell reponses in hepatitis C virus infection

World Journal of Gastroenterology

Volumn 13, Issue 36, 2007, Pages 4831-4838

  Semmo, Nasser ^a   Klenerman, Paul ^b  

^a UNIVERSITY OF FREIBURG   (Germany)

^b UNIVERSITY OF OXFORD   (United Kingdom)

Author keywords

CD4 T cells; Cytokines; Escape; Exhaustion; Hepatitis C virus; HLA class II; Immune responses; Interleukin 2; Proliferation

Indexed keywords

EPITOPE; HLA ANTIGEN CLASS 2; HLA DQB1 ANTIGEN; HLA DR ANTIGEN; NONSTRUCTURAL PROTEIN 3;

ALLELE; CD4+ T LYMPHOCYTE; CELL SPECIFICITY; CELLULAR IMMUNITY; GENE SEQUENCE; GENE TARGETING; HELPER CELL; HEPATITIS C; HEPATITIS C VIRUS; HUMAN; LIVER CELL CARCINOMA; LIVER CIRRHOSIS; MORBIDITY; MORTALITY; NONHUMAN; PERSISTENT VIRUS INFECTION; REGULATORY T LYMPHOCYTE; REVIEW; SEQUENCE ANALYSIS; TREATMENT OUTCOME; VIRUS MUTATION;

EID: 34848852702     PISSN: 10079327     EISSN: None     Source Type: Journal    
DOI: 10.3748/wjg.v13.i36.4831     Document Type: Review

References (71)

1. Gremion C, Cerny A. Hepatitis C virus and the immune system: a concise review. Rev Med Virol 2005; 15: 235-268
2. Grakoui A, Shoukry NH, Woollard DJ, Han JH, Hanson HL, Ghrayeb J, Murthy KK, Rice CM, Walker CM. HCV persistence and immune evasion in the absence of memory T cell help. Science 2003; 302: 659-662
3. Thimme R, Bukh J, Spangenberg HC, Wieland S, Pemberton J, Steiger C, Govindarajan S, Purcell RH, Chisari FV. Viral and immunological determinants of hepatitis C virus clearance, persistence, and disease. Proc Natl Acad Sci USA 2002; 99: 15661-15668
4. Gerlach JT, Diepolder HM, Jung MC, Gruener NH, Schraut WW, Zachoval R, Hoffmann R, Schirren CA, Santantonio T, Pape GR. Recurrence of hepatitis C virus after loss of virus-specific CD4(+) T-cell response in acute hepatitis C. Gastroenterology 1999; 117: 933-941
5. Missale G, Bertoni R, Lamonaca V, Valli A, Massari M, Mori C, Rumi MG, Houghton M, Fiaccadori F, Ferrari C. Different clinical behaviors of acute hepatitis C virus infection are associated with different vigor of the anti-viral cell-mediated immune response. J Clin Invest 1996; 98: 706-714
6. Thimme R, Oldach D, Chang KM, Steiger C, Ray SC, Chisari FV. Determinants of viral clearance and persistence during acute hepatitis C virus infection. J Exp Med 2001; 194: 1395-1406
7. Ulsenheimer A, Gerlach JT, Gruener NH, Jung MC, Schirren CA, Schraut W, Zachoval R, Pape GR, Diepolder HM. Detection of functionally altered hepatitis C virus-specific CD4 T cells in acute and chronic hepatitis C. Hepatology 2003; 37: 1189-1198
8. Ulsenheimer A, Lucas M, Seth NP, Tilman Gerlach J, Gruener NH, Loughry A, Pape GR, Wucherpfennig KW, Diepolder HM, Klenerman P. Transient immunological control during acute hepatitis C virus infection: ex vivo analysis of helper T-cell responses. J Viral Hepat 2006; 13: 708-714
9. Aberle JH, Formann E, Steindl-Munda P, Weseslindtner L, Gurguta C, Perstinger G, Grilnberger E, Laferl H, Dienes HP, Popow-Kraupp T, Ferenci P, Holzmann H. Prospective study of viral clearance and CD4(+) T-cell response in acute hepatitis C primary infection and reinfection. J Clin Virol 2006; 36: 24-31
10. Diepolder HM, Zachoval R, Hoffmann RM, Wierenga EA, Santantonio T, Jung MC, Eichenlaub D, Pape GR. Possible mechanism involving T-lymphocyte response to non-structural protein 3 in viral clearance in acute hepatitis C virus infection. Lancet 1995; 346: 1006-1007
11. Day CL, Lauer GM, Robbins GK, McGovern B, Wurcel AG, Gandhi RT, Chung RT, Walker BD. Broad specificity of virus-specific CD4+ T-helper-cell responses in resolved hepatitis C virus infection. J Virol 2002; 76: 12584-12595
12. Lamonaca V, Missale G, Urbani S, Pilli M, Born C, Mori C, Sette A, Massari M, Southwood S, Bertoni R, Valli A, Fiaccadori F, Ferrari C. Conserved hepatitis C virus sequences are highly immunogenic for CD4(+) T cells: implications for vacine development. Hepatology 1999; 30: 1088-1098
13. Shoukry NH, Sidney J, Sette A, Walker CM. Conserved hierarchy of helper T cell responses in a chimpanzee during primary and secondary hepatitis C virus infections. J Immunol 2004; 172: 483-492
14. Diepolder HM, Gerlach JT, Zachoval R, Hoffmann RM, Jung MC, Wierenga EA, Scholz S, Santantonio T, Houghton M, Southwood S, Sette A, Pape GR. Immunodominant CD4+ T-cell epitope within nonstructural protein 3 in acute hepatitis C virus infection. J Virol 1997; 71: 6011-6019
15. Lechner F, Wong DK, Dunbar PR, Chapman R, Chung RT, Dohrenwend P, Robbins G, Phillips R, Klenerman P, Walker BD. Analysis of successful immune responses in persons infected with hepatitis C virus. J Exp Med 2000; 191: 1499-1512
16. Rosen HR, Miner C, Sasaki AW, Lewinsohn DM, Conrad AJ, Bakke A, Bouwer HG, Hinrichs DJ. Frequencies of HCV-specific effector CD4+ T cells by flow cytometry: correlation with clinical disease stages. Hepatology 2002; 35: 190-198
17. Takaki A, Wiese M, Maertens G, Depla E, Seifert U, Liebetrau A, Miller JL, Manns MP, Rehermann B. Cellular immune responses persist and humoral responses decrease two decades after recovery from a single-source outbreak of hepatitis C. Nat Med 2000; 6: 578-582
18. Diepolder HM, Zachoval R, Hoffmann RM, Wierenga EA, Santantonio T, Jung MC, Eichenlaub D, Pape GR. Possible mechanism involving T-lymphocyte response to non-structural protein 3 in viral clearance in acute hepatitis C virus infection. Lancet 1995; 346: 1006-1007
19. Gerlach JT, Ulsenheimer A, Gruner NH, Jung MC, Schraut W, Schirren CA, Heeg M, Scholz S, Witter K, Zahn R, Vogler A, Zachoval R, Pape GR, Diepolder HM. Minimal T-cell-stimulatory sequences and spectrum of HLA restriction of immunodominant CD4+ T-cell epitopes within hepatitis C virus NS3 and NS4 proteins. J Virol 2005; 79: 12425-12433
20. Lucas M, Ulsenheimer A, Pfafferot K, Heeg MH, Gaudieri S, Gruner N, Rauch A, Gerlach JT, Jung MC, Zachoval R, Pape GR, Schraut W, Santantonio T, Nitschko H, Obermeier M, Phillips R, Scriba TJ, Semmo N, Day C, Weber JN, Fidler S, Thimme R, Haberstroh A, Baumert TF, Klenerman P, Diepolder HM. Iracking virus-specific CD4+ T cells during and after acute hepatitis C virus infection. PLoS ONE 2007; 2: e649
21. Fanning LJ, Levis J, Kenny-Walsh E, Whelton M, O'Sullivan K, Shanahan F. HLA class II genes determine the natural variance of hepatitis C viral load. Hepatology 2001; 33: 224-230
22. Alric L, Fort M, Izopet J, Vinel JP, Charlet JP, Selves J, Puel J, Pascal JP, Duffaut M, Abbal M. Genes of the major histocompatibility complex class II influence the outcome of hepatitis C virus infection. Gastroenterology 1997; 113: 1675-1681
23. Minton EJ, Smillie D, Neal KR, Irving WL, Underwood JC, James V. Association between MHC class II alleles and clearance of circulating hepatitis C virus. Members of the Trent Hepatitis C Virus Study Group. J Infect Dis 1998; 178: 39-44
24. Thursz M, Yallop R, Goldin R, Trepo C, Thomas HC. Influence of MHC class II genotype on outcome of infection with hepatitis C virus. The HENCORE group. Hepatitis C European Network for Cooperative Research. Lancet 1999; 354: 2119-2124
25. Harcourt G, Hellier S, Bunce M, Satsangi J, Collier J, Chapman R, Phillips R, Klenerman P. Effect of HLA class II genotype on T helper lymphocyte responses and viral control in hepatitis C virus infection. J Viral Hepat 2001; 8: 174-179
26. Godkin A, Jeanguet N, Thursz M, Openshaw P, Thomas H. Characterization of novel HLA-DR11-restricted HCV epitopes reveals both qualitative and quantitative differences in HCV-specific CD4+ T cell responses in chronically infected and non-viremic patients. Eur J Immunol 2001; 31: 1438-1446
27. Harcourt GC, Lucas M, Sheridan I, Barnes E, Phillips R, Klenerman P. Longitudinal mapping of protective CD4+ T cell responses against HCV: analysis of fluctuating dominant and subdominant HLA-DR11 restricted epitopes. J Viral Hepat 2004; 11: 324-331
28. Tsai SL, Liaw YF, Chen MH, Huang CY, Kuo GC. Detection of type 2-like T-helper cells in hepatitis C virus infection: implications for hepatitis C virus chronicity. Hepatology 1997; 25: 449-458
29. Wertheimer AM, Miner C, Lewinsohn DM, Sasaki AW, Kaufman E, Rosen HR. Novel CD4+ and CD8+ T-cell determinants within the NS3 protein in subjects with spontaneously resolved HCV infection. Hepatology 2003; 37: 577-589
30. Younes SA, Yassine-Diab B, Dumont AR, Boulassel MR, Grossman Z, Routy JP, Sekaly RP. HIV-1 viremia prevents the establishment of interleukin 2-producing HIV-specific memory CD4+ T cells endowed with proliferative capacity. J Exp Med 2003; 198: 1909-1922
31. Iyasere C, Tilton JC, Johnson AJ, Younes S, Yassine-Diab B, Sekaly RP, Kwok WW, Migueles SA, Laborico AC, Shupert WL, Hallahan CW, Davey RT Jr, Dybul M, Vogel S, Metcalf J, Connors M. Diminished proliferation of human immunodeficiency virus-specific CD4+ T cells is associated with diminished interleukin-2 (IL-2) production and is recovered by exogenous IL-2. J Virol 2003; 77: 10900-10909
32. Wherry EJ, Teichgraber V, Becker TC, Masopust D, Kaech SM, Antia R, von Andrian UH, Ahmed R. Lineage relationship and protective immunity of memory CD8 T cell subsets. Nat Immunol 2003; 4: 225-234
33. Fuller MJ, Zajac AJ. Ablation of CD8 and CD4 T cell responses by high viral loads. J Immunol 2003; 170: 477-486
34. Semmo N, Krashias G, Willberg C, Klenerman P. Analysis of the relationship between cytokine secretion and proliferative capacity in hepatitis C virus infection. J Viral Hepat 2007; 14: 492-502
35. Semmo N, Day CL, Ward SM, Lucas M, Harcourt G, Loughry A, Klenerman P. Preferential loss of IL-2-secreting CD4+ T helper cells in chronic HCV infection. Hepatology 2005; 41: 1019-1028
36. Day CL, Seth NP, Lucas M, Appel H, Gauthier L, Lauer GM, Robbins GK, Szczepiorkowski ZM, Casson DR, Chung RT, Bell S, Harcourt G, Walker BD, Klenerman P, Wucherpfennig KW. Ex vivo analysis of human memory CD4 T cells specific for hepatitis C virus using MHC class II tetramers. J Clin Invest 2003; 112: 831-842
37. Minutello MA, Pileri P, Unutmaz D, Censini S, Kuo G, Houghton M, Brunetto MR, Bonino F, Abrignani S. Compartmentalization of T lymphocytes to the site of disease: intrahepatic CD4+ T cells specific for the protein NS4 of hepatitis C virus in patients with chronic hepatitis C. J Exp Med 1993; 178: 17-25
38. Penna A, Missale G, Lamonaca V, Pilli M, Mori C, Zanelli P, Cavalli A, Elia G, Ferrari C. Intrahepatic and circulating HLA class II-restricted, hepatitis C virus-specific T cells: functional characterization in patients with chronic hepatitis C. Hepatology 2002; 35: 1225-1236
39. Schirren CA, Jung MC, Gerlach JT, Worzfeld T, Baretton G, Mamin M, Hubert Gruener N, Houghton M, Pape GR. Liver-derived hepatitis C virus (HCV)-specific CD4(+) T cells recognize multiple HCV epitopes and produce interferon gamma. Hepatology 2000; 32: 597-603
40. Harcourt GC, Lucas M, Godkin AJ, Kantzanou M, Phillips RE, Klenerman P. Evidence for lack of cross-genotype protection of CD4+ T cell responses during chronic hepatitis C virus infection. Clin Exp Immunol 2003; 131: 122-129
41. Lauer GM, Barnes E, Lucas M, Timm J, Ouchi K, Kim AY, Day CL, Robbins GK, Casson DR, Reiser M, Dusheiko G, Allen TM. Chung RT, Walker BD, Klenerman P. High resolution analysis of cellular immune responses in resolved and persistent hepatitis C virus infection. Gastroenterology 2004; 127: 924-936
42. Nelson DR, Tu Z, Soldevila-Pico C, Abdelmalek M, Zhu H, Xu YL, Cabrera R, Liu C, Davis GL. Long-term interleukin 10 therapy in chronic hepatitis C patients has a proviral and antiinflammatory effect. Hepatology 2003; 38: 859-868
43. Bain C, Fatmi A, Zoulim F, Zarski JP, Trepo C, Inchauspe G. Impaired allostimulatory function of dendritic cells in chronic hepatitis C infection. Gastroenterology 2001; 120: 512-524
44. Fowler NL, Torresi J, Jackson DC, Brown LE, Gowans EJ. Immune responses in hepatitis C virus infection: the role of dendritic cells. Immunol Cell Biol 2003; 81: 63-66
45. Lauer GM, Nguyen TN, Day CL, Robbins GK, Flynn T, McGowan K, Rosenberg ES, Lucas M, Klenerman P, Chung RT, Walker BD. Human immunodeficiency virus type 1-hepatitis C virus coinfection: intraindividual comparison of cellular inunune responses against two persistent viruses. J Virol 2002; 76: 2817-2826
46. Harcourt G, Gomperts E, Donfield S, Klenerman P. Diminished frequency of hepatitis C virus specific interferon {gamma} secreting CD4+ T cells in human immunodeficiency virus/hepatitis C virus coinfected patients. Gut 2006; 55: 1484-1487
47. Erickson AL, Kimura Y, Igarashi S, Eichelberger J, Houghton M, Sidney J, McKinney D, Sette A, Hughes AL, Walker CM. The outcome of hepatitis C virus infection is predicted by escape mutations in epitopes targeted by cytotoxic T lymphocytes. Immunity 2001; 15: 883-895
48. Vogel TU, Friedrich TC, O'Connor DH, Rehrauer W, Dodds EJ, Hickman H, Hildebrand W, Sidney J, Sette A, Hughes A, Horton H, Vielhuber K, Rudersdorf R, De Souza IP, Reynolds MR, Allen TM, Wilson N, Watkins DI. Escape in one of two cytotoxic T-lymphocyte epitopes bound by a high-frequency major histocompatibility complex class I molecule, Mamu-A*02: a paradigm for virus evolution and persistence? J Virol 2002; 76: 11623-11636
49. O'Connor DH, Allen TM, Vogel TU, Jing P, DeSouza IP, Dodds E, Dunphy EJ, Melsaether C, Mothe B, Yamamoto H, Horton H, Wilson N, Hughes AL, Watkins DI. Acute phase cytotoxic T lymphocyte escape is a hallmark of simian immunodeficiency virus infection. Nat Med 2002; 8: 493-499
50. Allen TM, O'Connor DH, Jing P, Dzuris JL, Mothe BR, Vogel TU, Dunphy E, Liebl ME, Emerson C, Wilson N, Kunstman KJ, Wang X, Allison DB, Hughes AL, Desrosiers RC, Altman JD, Wolinsky SM, Sette A, Watkins DI. Tat-specific cytotoxic T lymphocytes select for SIV escape variants during resolution of primary viraemia. Nature 2000; 407: 386-390
51. Altfeld M, Allen TM, Yu XG, Johnston MN, Agrawal D, Korber BT, Montefiori DC, O'Connor DH, Davis BT, Lee PK, Maier EL, Harlow J, Goulder PJ, Brander C, Rosenberg ES, Walker BD. HIV-1 superinfection despite broad CD8+ T-cell responses containing replication of the primary virus. Nature 2002; 420: 434-439
52. Goulder PJ, Phillips RE, Colbert RA, McAdam S, Ogg G, Nowak MA, Giangrande P, Luzzi G, Morgan B, Edwards A, McMichael AJ, Rowland-Jones S. Late escape from an immunodominant cytotoxic T-lymphocyte response associated with progression to AIDS. Nat Med 1997; 3: 212-217
53. Borrow P, Lewicki H, Wei X, Horwitz MS, Peffer N, Meyers H, Nelson JA, Gairin JE, Hahn BH, Oldstone MB, Shaw GM. Antiviral pressure exerted by HIV-1-specific cytotoxic T lymphocytes (CTLs) during primary infection demonstrated by rapid selection of CTL escape virus. Nat Med 1997; 3: 205-211
54. von Hahn T, Yoon JC, Alter H, Rice CM, Rehermann B, Balfe P, McKeating JA. Hepatitis C virus continuously escapes from neutralizing antibody and T-cell responses during chronic infection in vivo. Gastroenterology 2007; 132: 667-678
55. Wang H, Eckels DD. Mutations in immunodominant T cell epitopes derived from the nonstructural 3 protein of hepatitis C virus have the potential for generating escape variants that may have important consequences for T cell recognition. J Immunol 1999; 162: 4177-4183
56. Harcourt GC, Garrard S, Davenport MP, Edwards A, Phillips RE. HIV-1 variation diminishes CD4 T lymphocyte recognition. J Exp Med 1998; 188: 1785-1793
57. Eckels DD, Zhou H, Bian TH, Wang H. Identification of antigenic escape variants in an immunodominant epitope of hepatitis C virus. Int Immunol 1999; 11: 577-583
58. Wang JH, Layden TJ, Eckels DD. Modulation of the peripheral T-Cell response by CD4 mutants of hepatitis C virus: transition from a Th1 to a Th2 response. Hum Immunol 2003; 64: 662-673
59. Puig M, Mihalik K, Tilton JC, Williams O, Merchlinsky M, Connors M, Feinstone SM, Major ME. CD4+ immune escape and subsequent T-cell failure following chimpanzee immunization against hepatitis C virus. Hepatalogy 2006; 44: 736-745
60. Parren PW, Moore JP, Burton DR, Sattentau QJ. The neutralizing antibody response to HIV-1: viral evasion and escape from humoral immunity. AIDS 1999; 13 Suppl A: S137-S162
61. Ciurea A, Klenerman P, Hunziker L, Horvath E, Senn BM, Ochsenbein AF, Hengartner H, Zinkernagel RM. Viral persistence in vivo through selection of neutralizing antibody-escape variants. Proc Natl Acad Sci USA 2000; 97: 2749-2754
62. Ciurea A, Hunziker L, Klenerman P, Hengartner H, Zinkernagel RM. Impairment of CD4(+) T cell responses during chronic virus infection prevents neutralizing antibody responses against virus escape mutants. J Exp Med 2001; 193: 297-305
63. Gallimore A, Glithero A, Godkin A, Tissot AC, Pluckthun A, Elliott T, Hengartner H, Zinkernagel R. Induction and exhaustion of lymphocytic choriomeningitis virus-specific cytotoxic T lymphocytes visualized using soluble tetrameric major histocompatibility complex class I-peptide complexes. J Exp Med 1998; 187: 1383-1393
64. Moskopbidis D, Lechner F, Pircher H, Zinkernagel RM. Virus persistence in acutely infected immunocompetent mice by exhaustion of antiviral cytotoxic effector T cells. Nature 1993; 362: 758-761
65. Rouse BT, Sarangi PP, Suvas S. Regulatory T cells in virus infections. Immunol Rev 2006; 212: 272-286
66. Rushbrook SM, Ward SM, Unitt E, Vowler SL, Lucas M, Klenerman P, Alexander GJ. Regulatory T cells suppress in vitro proliferation of virus-specific CD8+ T cells during persistent hepatitis C virus infection. J Virol 2005; 79: 7852-7859
67. Boettler T, Spangenberg HC, Neumann-Haefelin C, Panther E, Urbani S, Ferrari C, Blum HE, von Weizsacker F, Thimme R. 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 2005; 79: 7860-7867
68. Cabrera R, Tu Z, Xu Y, Firpi RJ, Rosen HR, Liu C, Nelson DR. An immunomodulatory role for CD4(+)CD25(+) regulatory T lymphocytes in hepatitis C virus infection. Hepatology 2004; 40: 1062-1071
69. Sugimoto K, Ikeda F, Stadanlick J, Nunes FA, Alter HJ, Chang KM. Suppression of HCV-specific T cells without differential hierarchy demonstrated ex vivo in persistent HCV infection. Hepatology 2003; 38: 1437-1448
70. Bolacchi F, Sinistro A, Ciaprini C, Demin F, Capozzi M, Carducci FC, Drapeau CM, Rocchi G, Bergamini A. Increased hepatitis C virus (HCV)-specific CD4+CD25+ regulatory T lymphocytes and reduced HCV-specific CD4+ T cell response in HCV-infected patients with normal versus abnormal alanine aminotransferase levels. Clin Exp Immunol 2006; 144: 188-196
71. Ward SM, Fox BC, Brown PJ, Worthington J, Fox SB, Chapman RW, Fleming KA, Banham AH, Klenerman P. Quantification and localisation of FOXP3+ T lymphocytes and relation to hepatic inflammation during chronic HCV infection. J Hepatol 2007; 47: 316-324