Journal of Hepatology
Volume 46, Issue 3 , Pages 508-520 , March 2007

Immunological techniques in viral hepatitis

  • Barbara Rehermann

      Affiliations

    • Immunology Section, Liver Diseases Branch NIDDK, National Institutes of Health, DHHS, 10 Center Drive, Room 9B16, Bethesda, MD 20892, USA
    • Corresponding Author InformationCorresponding authors. Tel.: +1 301 402 7144; fax: +1 301 402 0491 (B. Rehermann), tel.: +44 20 7679 6512; fax: +44 20 7380 0405 (N.V. Naoumov).
    • ,
  • Nikolai V. Naoumov

      Affiliations

    • Institute of Hepatology, University College London, 69-75 Chenies Mews, London WC1E 6HX, UK
    • Corresponding Author InformationCorresponding authors. Tel.: +1 301 402 7144; fax: +1 301 402 0491 (B. Rehermann), tel.: +44 20 7679 6512; fax: +44 20 7380 0405 (N.V. Naoumov).

References 

  1. Ferrari C, Mondelli MU, Penna A, Faccadori F, Chisari FV. Functional characterization of cloned intrahepatic, hepatitis B virus nucleoprotein-specific helper T cell lines. J Immunol. 1987;139:539–544
  2. Barnaba V, Franco A, Alberti A, Balsano C, Benvenuto R, Balsano F. Recognition of hepatitis B envelope proteins by liver-infiltrating T lymphocytes in chronic HBV infection. J Immunol. 1989;143:2650–2655
  3. Mondelli MU, Chisari FV, Ferrari C. The cellular immune response to nucleocapsid antigens in hepatitis B virus infection. Springer Semin Immunopathol. 1990;12:25–31
  4. Diepolder HM, Gerlach J-T, Zachoval R, Hoffmann RM, Jung MC, Wierenga EA, et al. Immunodominant CD4+ T-cell epitope within nonstructural protein 3 in acute hepatitis C virus infection. J Virol. 1997;71:6011–6019
  5. Cooper S, Erickson AL, Adams EJ, Kansopon J, Weiner AJ, Chien DY, et al. Analysis of a successful immune response against hepatitis C virus. Immunity. 1999;10:439–449
  6. Erickson AL, Kimura Y, Igarashi S, Eichelberger J, Houghton M, Sidney J, et al. The outcome of hepatitis C virus infection is predicted by escape mutations in epitopes targeted by cytotoxic T lymphocytes. Immunity. 2001;15:883–895
  7. Bertoletti A, Ferrari C, Fiaccadori F, Penna A, Margolskee R, Schlicht HJ, et al. HLA class-I restricted human cytotoxic T cells recognize endogenously synthesized hepatitis B virus nucleocapsid antigen. Proc Natl Acad Sci USA. 1991;88:10445–10449
  8. Koziel MJ, Dudley D, Wong JT, Dienstag J, Houghton M, Ralston R, et al. Intrahepatic cytotoxic T lymphocytes specific for hepatitis C virus in persons with chronic hepatitis. J Immunol. 1992;149:3339–3344
  9. Barnaba V, Franco A, Alberti A, Benvenuto R, Balsano F. Selective killing of hepatitis B envelope antigen-specific B cells by class I restricted, exogenous antigen specific T lymphocytes. Nature. 1990;345:258–260
  10. Koziol JA, Ferrari C, Chisari FV. Evaluation of monoclonality of cell lines from sequential dilution assays. J Immunol Methods. 1987;105:139–143
  11. Rehermann B, Chang KM, McHutchison JG, Kokka R, Houghton M, Chisari FV. Quantitative analysis of the peripheral blood cytotoxic T lymphocyte response, disease activity and viral load in patients with chronic hepatitis C virus infection. J Clin Invest. 1996;98:1432–1440
  12. Lechner F, Wong DK, Dunbar PR, Chapman R, Chung RT, Dohrenwend P, et al. Analysis of successful immune responses in persons infected with hepatitis C virus. J Exp Med. 2000;191:1499–1512
  13. Day CL, Lauer GM, Robbins GK, McGovern B, Wurcel AG, Gandhi RT, et al. Broad specificity of virus-specific CD4+ T-helper-cell responses in resolved hepatitis C virus infection. J Virol. 2002;76:12584–12595
  14. Lauer GM, Ouchi K, Chung RT, Nguyen TN, Day CL, Purkis DR, et al. Comprehensive analysis of CD8(+)-T-cell responses against hepatitis C virus reveals multiple unpredicted specificities. J Virol. 2002;76:6104–6113
  15. Maecker HT, Moon J, Bhatia S, Ghanekar SA, Maino VC, Payne JK, et al. Impact of cryopreservation on tetramer, cytokine flow cytometry, and ELISPOT. BMC Immunol. 2005;6:17
  16. Garcia-Pineres AJ, Hildesheim A, Williams M, Trivett M, Strobl S, Pinto LA. DNAse treatment following thawing of cryopreserved PBMC is a procedure suitable for lymphocyte functional studies. J Immunol Methods. 2006;313:209–213
  17. Czerkinsky CC, Nilsson LA, Nygren H, Ouchterlony O, Tarkowski A. A solid-phase enzyme-linked immunospot (ELISPOT) assay for enumeration of specific antibody-secreting cells. J Immunol Methods. 1983;65:109–121
  18. Czerkinsky C, Andersson G, Ekre HP, Nilsson LA, Klareskog L, Ouchterlony O. Reverse ELISPOT assay for clonal analysis of cytokine production. I. Enumeration of gamma-interferon-secreting cells. J Immunol Methods. 1988;110:29–36
  19. Gazagne A, Claret E, Wijdenes J, Yssel H, Bousquet F, Levy E, et al. A Fluorospot assay to detect single T lymphocytes simultaneously producing multiple cytokines. J Immunol Methods. 2003;283:91–98
  20. Kreher CR, Dittrich MT, Guerkov R, Boehm BO, Tary-Lehmann M. CD4+ and CD8+ cells in cryopreserved human PBMC maintain full functionality in cytokine ELISPOT assays. J Immunol Methods. 2003;278:79–93
  21. Karulin AY, Hesse MD, Tary-Lehmann M, Lehmann PV. Single-cytokine-producing CD4 memory cells predominate in type 1 and type 2 immunity. J Immunol. 2000;164:1862–1872
  22. McCutcheon M, Wehner N, Wensky A, Kushner M, Doan S, Hsiao L, et al. A sensitive ELISPOT assay to detect low-frequency human T lymphocytes. J Immunol Methods. 1997;210:149–166
  23. Maecker HT, Dunn HS, Suni MA, Khatamzas E, Pitcher CJ, Bunde T, et al. Use of overlapping peptide mixtures as antigens for cytokine flow cytometry. J Immunol Methods. 2001;255:27–40
  24. Draenert R, Altfeld M, Brander C, Basgoz N, Corcoran C, Wurcel AG, et al. Comparison of overlapping peptide sets for detection of antiviral CD8 and CD4 T cell responses. J Immunol Methods. 2003;275:19–29
  25. Firbas C, Jilma B, Tauber E, Buerger V, Jelovcan S, Lingnau K, et al. Immunogenicity and safety of a novel therapeutic hepatitis C virus (HCV) peptide vaccine: a randomized, placebo controlled trial for dose optimization in 128 healthy subjects. Vaccine. 2006;24:4343–4353
  26. Wedemeyer H, He X-S, Nascimbeni M, Davis AR, Greenberg HB, Hoofnagle JH, et al. Impaired effector function of hepatitis C virus-specific CD8+ T cells in chronic hepatitis C virus infection. J Immunol. 2002;169:3447–3458
  27. Guerkov RE, Targoni OS, Kreher CR, Boehm BO, Herrera MT, Tary-Lehmann M, et al. Detection of low-frequency antigen-specific IL-10-producing CD4(+) T cells via ELISPOT in PBMC: cognate vs. nonspecific production of the cytokine. J Immunol Methods. 2003;279:111–121
  28. Nylander S, Kalies I. Brefeldin A, but not monensin, completely blocks CD69 expression on mouse lymphocytes: efficacy of inhibitors of protein secretion in protocols for intracellular cytokine staining by flow cytometry. J Immunol Methods. 1999;224:69–76
  29. Suni MA, Dunn HS, Orr PL, de Laat R, Sinclair E, Ghanekar SA, et al. Performance of plate-based cytokine flow cytometry with automated data analysis. BMC Immunol. 2003;4:9
  30. Riedy MC, Muirhead KA, Jensen CP, Stewart CC. Use of a photolabeling technique to identify nonviable cells in fixed homologous or heterologous cell populations. Cytometry. 1991;12:133–139
  31. King MA. Detection of dead cells and measurement of cell killing by flow cytometry. J Immunol Methods. 2000;243:155–166
  32. Fetterhoff T, Holland S, Wile K. Fluorescent detection of non-viable cells in fixed cell preparations. Cytometry. 1993;Suppl. 6:27
  33. Day CL, Seth NP, Lucas M, Appel H, Gauthier L, Lauer GM, et al. 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
  34. Maini MK, Boni C, Lee CK, Larrubia JR, Reignat S, Ogg GS, et al. The role of virus-specific CD8+ cells in liver damage and viral control during persistent hepatitis B virus (HBV) infection. J Exp Med. 2000;191:1269–1280
  35. He X-S, Rehermann B, Lopez-Labrador FX, Boisvert J, Cheung R, Mumm J, et al. Quantitative analysis of hepatitis C virus-specific CD8(+) T cells in peripheral blood and liver using peptide-MHC tetramers. Proc Natl Acad Sci USA. 1999;96:5692–5697
  36. Accapezzato D, Francavilla V, Paroli M, Casciaro M, Chircu LV, Cividini A, et al. Hepatic expansion of a virus-specific regulatory CD8(+) T cell population in chronic hepatitis C virus infection. J Clin Invest. 2004;113:963–972
  37. Ulsenheimer A, Lucas M, Seth NP, Tilman Gerlach J, Gruener NH, Loughry A, et al. Transient immunological control during acute hepatitis C virus infection: ex vivo analysis of helper T-cell responses. J Viral Hepat. 2006;13:708–714
  38. Ferrari C, Penna A, Bertoletti A, Valli A, Antoni AD, Giuberti T, et al. Cellular immune response to hepatitis B virus-encoded antigens in acute and chronic hepatitis B virus infection. J Immunol. 1990;145:3442–3449
  39. Vento S, Rondanelli EG, Ranieri S, O’Brien CJ, Williams R, Eddleston AL. Prospective study of cellular immunity to hepatitis-B-virus antigens from the early incubation phase of acute hepatitis B. Lancet. 1987;2:119–122
  40. Diepolder HM, Zachoval R, Hoffmann RM, Wierenga A, Santantonio T, Jung M-C, et al. 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
  41. Rigopoulou EI, Suri D, Chokshi S, Mullerova I, Rice S, Tedder RS, et al. Lamivudine plus interleukin-12 combination therapy in chronic hepatitis B: antiviral and immunological activity. Hepatology. 2005;42:1028–1036
  42. Harari A, Dutoit V, Cellerai C, Bart PA, Du Pasquier RA, Pantaleo G. Functional signatures of protective antiviral T-cell immunity in human virus infections. Immunol Rev. 2006;211:236–254
  43. Liu L, Chahroudi A, Silvestri G, Wernett ME, Kaiser WJ, Safrit JT, et al. Visualization and quantification of T cell-mediated cytotoxicity using cell-permeable fluorogenic caspase substrates. Nat Med. 2002;8:185–189
  44. Betts MR, Brenchley JM, Price DA, De Rosa SC, Douek DC, Roederer M, et al. Sensitive and viable identification of antigen-specific CD8+ T cells by a flow cytometric assay for degranulation. J Immunol Methods. 2003;281:65–78
  45. Shafer-Weaver K, Rosenberg S, Strobl S, Gregory Alvord W, Baseler M, Malyguine A. Application of the granzyme B ELISPOT assay for monitoring cancer vaccine trials. J Immunother. 2006;29:328–335
  46. Zuber B, Levitsky V, Jonsson G, Paulie S, Samarina A, Grundstrom S, et al. Detection of human perforin by ELISpot and ELISA: ex vivo identification of virus-specific cells. J Immunol Methods. 2005;302:13–25
  47. Wolint P, Betts MR, Koup RA, Oxenius A. Immediate cytotoxicity but not degranulation distinguishes effector and memory subsets of CD8+ T cells. J Exp Med. 2004;199:925–936
  48. Koziel JM, Dudley D, Afdhal N, Choo QL, Houghton M, Ralston R, et al. Hepatitis C virus (HCV)-specific cytotoxic T lymphocytes recognize epitopes in the core and envelope proteins of HCV. J Virol. 1993;67:7522–7532
  49. Bertoletti A, Sette A, Chisari FV, Penna A, Levrero M, De Carli M, et al. Natural variants of cytotoxic epitopes are T-cell receptor antagonists for antiviral cytotoxic T cells. Nature. 1994;369:407–410
  50. Chang KM, Rehermann B, McHutchison JG, Pasquinelli C, Southwood S, Sette A, et al. Immunological significance of cytotoxic T lymphocyte epitope variants in patients chronically infected by the hepatitis C virus. J Clin Invest. 1997;100:2376–2385
  51. Meyer-Olson D, Shoukry NH, Brady KW, Kim H, Olson DP, Hartman K, et al. Limited T cell receptor diversity of HCV-specific T cell responses is associated with CTL escape. J Exp Med. 2004;200:307–319
  52. Urbani S, Amadei P, Fisicaro P, Massimo P, Missale G, Bertoletti A, et al. Heterologous T cell immunity in severe hepatitis C virus (HCV) infection. J Exp Med. 2005;201:675–680
  53. Rosa D, Saletti G, De Gregorio E, Zorat F, Comar C, D’Oro U, et al. Activation of naive B lymphocytes via CD81, a pathogenetic mechanism for hepatitis C virus-associated B lymphocyte disorders. Proc Natl Acad Sci USA. 2005;102:18544–18549
  54. Bernasconi NL, Traggiai E, Lanzavecchia A. Maintenance of serological memory by polyclonal activation of human memory B cells. Science. 2002;298:2199–2202
  55. Poeck H, Wagner M, Battiany J, Rothenfusser S, Wellisch D, Hornung V, et al. Plasmacytoid dendritic cells, antigen, and CpG-C license human B cells for plasma cell differentiation and immunoglobulin production in the absence of T-cell help. Blood. 2004;103:3058–3064
  56. Bartosch B, Dubuisson J, Cosset FL. Infectious hepatitis C virus pseudo-particles containing functional E1-E2 envelope protein complexes. J Exp Med. 2003;197:633–642
  57. Hsu M, Zhang J, Flint M, Logvinoff C, Cheng-Mayer C, Rice CM, et al. Hepatitis C virus glycoproteins mediate pH-dependent cell entry of pseudotyped retroviral particles. Proc Natl Acad Sci USA. 2003;100:7271–7276
  58. Lindenbach BD, Evans MJ, Syder AJ, Wolk B, Tellinghuisen TL, Liu CC, et al. Complete replication of hepatitis C virus in cell culture. Science. 2005;309:623–626
  59. Wakita T, Pietschmann T, Kato T, Date T, Miyamoto M, Zhao Z, et al. Production of infectious hepatitis C virus in tissue culture from a cloned viral genome. Nat Med. 2005;11:791–796
  60. Zhong J, Gastaminza P, Cheng G, Kapadia S, Kato T, Burton DR, et al. Robust hepatitis C virus infection in vitro. Proc Natl Acad Sci USA. 2005;102:9294–9299
  61. Dreux M, Pietschmann T, Granier C, Voisset C, Ricard-Blum S, Mangeot PE, et al. High density lipoprotein inhibits hepatitis C virus-neutralizing antibodies by stimulating cell entry via activation of the scavenger receptor BI. J Biol Chem. 2006;281:18285–18295
  62. Voisset C, Op de Beeck A, Horellou P, Dreux M, Gustot T, Duverlie G, et al. High-density lipoproteins reduce the neutralizing effect of hepatitis C virus (HCV)-infected patient antibodies by promoting HCV entry. J Gen Virol. 2006;87:2577–2581
  63. Tang KH, Herrmann E, Cooksley H, Tatman N, Chokshi S, Williams R, et al. Relationship between early HCV kinetics and T-cell reactivity in chronic hepatitis C genotype 1 during peginterferon and ribavirin therapy. J Hepatol. 2005;43:776–782
  64. Mullan B, Kenny-Walsh E, Collins JK, Shanahan F, Fanning LJ. Inferred hepatitis C virus quasispecies diversity is influenced by choice of DNA polymerase in reverse transcriptase-polymerase chain reactions. Anal Biochem. 2001;289:137–146
  65. Smith DB, McAllister J, Casino C, Simmonds P. Virus ’quasispecies’: making a mountain out of a molehill?. J Gen Virol. 1997;78(Pt 7):1511–1519
  66. Kwok S, Higuchi R. Avoiding false-positives with polymerase chain reaction. Nature. 1989;339:237–238
  67. Bradley RD, Hillis DM. Recombinant DNA sequences generated by PCR amplification. Mol Biol Evol. 1997;14:592–593
  68. Liu SL, Rodrigo AG, Shankarappa R, Learn GH, Hsu L, Davidov O, et al. HIV quasispecies and resampling. Science. 1996;273:415–416
  69. Simmonds P, Bukh J, Combet C, Deleage G, Enomoto N, Feinstone S, et al. Consensus proposals for a unified system of nomenclature of hepatitis C virus genotypes. Hepatology. 2005;42:962–973
  70. Vogelstein B, Kinzler KW. Digital PCR. Proc Natl Acad Sci USA. 1999;96:9236–9241
  71. Ray SC, Fanning L, Wang XH, Netski DM, Kenny-Walsh E, Thomas DL. Divergent and convergent evolution after a common-source outbreak of hepatitis C virus. J Exp Med. 2005;201:1753–1759
  72. Cox AL, Mosbruger T, Mao Q, Liu Z, Wang XH, Yang HC, et al. Cellular immune selection with hepatitis C virus persistence in humans. J Exp Med. 2005;201:1741–1752
  73. MacDonald HR. NK1.1+ T cell receptor-alpha/beta+ cells: new clues to their origin, specificity, and function. J Exp Med. 1995;182:633–638
  74. Bendelac A, Lantz O, Quimby ME, Yewdell JW, Bennink JR, Brutkiewicz RR. CD1 recognition by mouse NK1+ T lymphocytes. Science. 1995;268:863–865
  75. Emoto M, Kaufmann SH. Liver NKT cells: an account of heterogeneity. Trends Immunol. 2003;24:364–369
  76. Exley M, Koziel M. To be or not to be NKT: Natural killer T cells in the liver. Hepatology. 2004;40:1033–1040
  77. Scheibenbogen C, Romero P, Rivoltini L, Herr W, Schmittel A, Cerottini JC, et al. Quantitation of antigen-reactive T cells in peripheral blood by IFNgamma-ELISPOT assay and chromium-release assay: a four-centre comparative trial. J Immunol Methods. 2000;244:81–89

PII: S0168-8278(07)00004-9

doi: 10.1016/j.jhep.2007.01.002

Journal of Hepatology
Volume 46, Issue 3 , Pages 508-520 , March 2007

Article Tools

* Image Usage & Resolution