8 Immunopathogenesis of hepatitis C

Biomedical Research Reports

Volumn 2, Issue C, 2000, Pages 147-168

  Rehermann, Barbara ^a  

^a NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 77957023855     PISSN: 18745326     EISSN: None     Source Type: Book Series    
DOI: 10.1016/S1874-5326(00)80012-5     Document Type: Article

References (169)

1. Booth J.C. Chronic hepatitis C: the virus, its discovery and the natural history of the disease. J Viral Hepatitis 5 (1998) 213-222
2. Mutimer D.J., Harrison R.F., O'Donnell K.B., et al. Hepatitis C virus infection in the asymptomatic British blood donor. J Viral Hepatitis 2 (1995) 47-53
3. Delaporte E., Thiers V., Dazza M.C., et al. High level of hepatitis C endemicity in Gabon, equatorial Africa. Trans R Soc Trop Med Hyg 87 (1993) 636-637
4. Saeed A.A., al-Admawi A.M., al-Rasheed A., et al. Hepatitis C virus infection in Egyptian volunteer blood donors in Riyadh. Lancet 338 (1991) 459-460
5. el-Ahmady O., Halim A.B., Mansour O., and Salman T. Incidence of hepatitis C virus in Egyptians. J Hepatol 21 (1994) 687
6. Alter M.J. Epidemiology of hepatitis C in the West. Semin Liver Dis 15 (1995) 5-14
7. Choo Q.-L., Kuo G., Weiner A.J., Overby L.R., Bradley D.W., and Houghton M. Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science 244 (1989) 359-362
8. Alter M.J., Margolis H.S., Krawczynski K., et al. The natural history of community-acquired hepatitis C in the United States. N Engl J Med 327 (1992) 1899-1905
9. Sansono D., and Dammacco F. Hepatitis C virus related chronic liver disease of sporadic type: clinical, serological and histological features. Digestion 51 (1992) 115-120
10. Oxenius A., Zinkernagel R.M., and Hengartner H. CD4+ T-cell induction and effector functions: a comparison of immunity against soluble antigens and viral infections. Adv Immunol 70 (1998) 313-367
11. Moretta L., Ciccone E., Mingari M.C., Biassoni R., and Moretta A. Human natural killer cells: origin, clonality, specificity, receptors. Adv Immunol 55 (1994) 341-358
12. Ludewig B., Ehl S., Karrer U., Odermatt B., Hengartner H., and Zinkernagel R.M. Dendritic cells efficiently induce protective antiviral immunity. J Virol 72 (1998) 3812-3818
13. Murali-Krishna K., Altman J.D., Suresh M., et al. Counting antigen-specific CD8 T cells: a re-evaluation of bystander activation during viral infection. Immunity 8 (1998) 177-187
14. Mosmann T.R., Cherwinski H., Bond M.W., Giedlin M.A., and Coffman R.L. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol 136 (1986) 2348-2357
15. Vitetta E.S., Fernandez-Botran R., Myers C.D., and Sanders V.M. Cellular interactions in the humoral immune response. Adv Immunol 45 (1989) 1-105
16. Doherty P.C., Allan W., and Eichelberger M. Roles of ab and gd T cell subsets in viral immunity. Annu Rev Immunol 10 (1992) 123-151
17. Kim J., Woods A., Becker-Dunn E., and Bottomly K. Distinct functional phenotypes of cloned Iarestricted helper T cells. J Exp Med 162 (1985) 188-201
18. Croen K.D. Evidence for an antiviral effect of nitric oxide. J Clin Invest 91 (1993) 2446-2452
19. Karupiah G., Xie Q.-W., Buller R.M.L., Nathan C., Duarte C., and MacMicking J.D. Inhibition of viral replication by interferon gamma induced nitric oxide synthased. Science 261 (1993) 1445-1448
20. Harris N., Buller R.M.L., and Karupiah G. Interferon-gamma induced, nitric oxide mediated inhibition of vaccinia viral replication. J Virol 69 (1995) 910-915
21. Sharara A.I., Perkins D.J., Misukonis M.A., Chan S.U., Dominitz J.A., and Weinberg J.B. Interferon (IFN)-alpha activation of human blood mononuclear cells in vitro and in vivo for nitric oxide synthase (NOS) type 2 mRNA and protein expression: possible relationship of induced NOS2 to the anti-hepatitis C effects of IFN-alpha in vivo. J Exp Med 186 (1997) 1495-1502
22. Nussler A.K., Di Silvio M., Billiar T.R., et al. Stimulation f the nitric oxide synthase pathway in human hepatocytes by cytokines and endotoxin. J Exp Med 176 (1992) 261-264
23. Farrar M.A., and Schreiber R.D. The molecular cell biology of interferon gamma and its receptor. Annu Rev Immunol 11 (1993) 571-611
24. Zinkernagel R.M., Moskophidis D., Kundig T., Oehen S., Pircher H.P., and Hengartner H. Effector T-cell induction and T-cell memory versus peripheral deletion of T cells. Immunol Rev 131 (1993) 198-223
25. Guidotti L.G., Ando K., Hobbs M.V., et al. Cytotoxic T lymphocytes inhibit hepatitis B virus gene expression by a noncytolytic mechanism in transgenic mice. Proc Natl Acad Sci USA 91 (1994) 3764-3768
26. Guidotti L.G., Ishikawa T., Hobbs M.V., Matzke B., Schreiber R., and Chisari F.V. Intracellular inactivation of the hepatitis B virus by cytotoxic T lymphocytes. Immunity 4 (1996) 35-36
27. Pavic I., Polic B., Crnkovic I., Lucin P., Jonjic S., and Koszinowki U.H. Participation of endogenous tumor necrosis factor alpha in host resistance to cytomegalovirus infection. J Gen Virol 74 (1993) 2215-2223
28. Franco M.A., Tin C., Rott L.S., Van Cotte J.L., McGhee J.R., and Greenberg H.B. Evidence for CD8+ T-cell immunity to murine rotavirus in the absence of perforin, fas and gamma interferon. J Virol 71 (1997) 479-486
29. Urban J.F.J., Katona I.M., Paul W.E., and Finkelman F.D. Interleukin-4 is important in protective immunity to a gastrointestinal nematode infection in mice. Proc Natl Acad Sci U S A 88 (1991) 5513-5517
30. Mosmann T.R., and Sad S. The expanding universe of T-cell subsets: Th1, Th2 and more. Immunol Today 17 (1996) 138-146
31. Abbas A.K., Murph K.M., and Sher A. Functional diversity of helper T lymphocytes. Nature 383 (1996) 787-793
32. Nagler A., Lanier L.L., and Phillips J.H. The effects of IL-4 on human natural killer cells: a potent regulator of IL-2 activation and proliferation. J Immunol 141 (1988) 2349-2351
33. Martinez O.M., Gibbons R.S., Garovoy M.R., and Aronson F.R. IL-4 inhibits IL-2 receptor expression and IL-2 dependent proliferation of human T cells. J Immunol 144 (1990) 2211-2215
34. Shearer G.M., and Clerici M. Cytokine profiles in HIV type 1 disease and protection. AIDS Res Hum Retroviruses 14 Suppl 2 (1998) S149-S152
35. Dai W.J., Bartens W., Kohler G., Hufnagel M., Kopf M., and Brombacher F. Impaired macrophage listericidal and cytokine activities are responsible for the rapid death of Listeria monocytogenes-infected IFN- gamma receptor-deficient mice. J Immunol 158 (1997) 5297-5304
36. Nakajima H., Iwamoto I., Tomoe S., et al. CD4+ T-lymphocytes and interleukin-5 mediate antigen-induced eosinophil infiltration into mouse trachea. Annu Rev Respir Dis 146 (1992) 374-377
37. Scott P., Pearce E., Cheever A., Coffman R., and Sher A. Role of cytokines and CD4+ T cell subsets in the regulation of parasitic immunity and disease. Innumol Rev 112 (1989) 161-182
38. Gazzinelli R.T., Hieny S., Wynn T.A., Wolf S., and Sher A. IL-12 is required for the T-lymphocyte-independent induction of interferon gamma by an intracellular parasite and induces resistance in T cell deficient hosts. Proc Natl Acad Sci U S A 90 (1993) 6115-6119
39. Sypek J.P., Chung C.L., Mayor S., et al. Resolution of cutaneous leishmaniasis: interleukin 12 initiates a protective T helper type 1 immune response. J Exp Med 177 (1993) 1797-1802
40. Tite J.P., Foellmer H.G., Mardi J.P., and Janeway Jr. C.A. Inverse Ir gene control of the antibody and T cell proliferative response to human basement membrane collagen. J Immunol 139 (1987) 2892-2898
41. Murray J.S., Madri J., Tite J., Carding S.R., and Bottomly K. MHC control of CD4+ T cell subset activation. J Exp Med 170 (1989) 2135-2140
42. Cai Z., and Sprent J. Influence of antigen dose and costimulation on the primary response of CD8+ T cells in vitro. J Exp Med 183 (1996) 2247-2257
43. Thompson C.B. Distinct roles for the costimulatory ligands B7-1 and B7-2 in T helper cell differentiation?. Cell 81 (1995) 979-982
44. Pfeiffer C., Stein J., Southwood S., Ketelaar H., Sette A., and Bottomly K. Altered peptide ligands can control CD4 T lymphocyte differentiation in vivo. J Exp Med 181 (1995) 1569-1574
45. Kawamura T., Furusaka A., Koziel M.J., et al. Transgenic expression of hepatitis C virus structural proteins in the mouse. Hepatology 25 (1997) 1014-1021
46. Pearson C.I., van Ewijk W., and McDevitt H.O. Induction of apoptosis and T helper 2 (Th2) responses correlates with peptide affinity for the major histocompatibility complex in self- reactive T cell receptor transgenic mice. J Exp Med 185 (1997) 583-599
47. Valitutti S., Müller S., Cella M., Padovan E., and Lanzavecchia A. Serial triggering of many T-cell receptors by a few peptide-MHC complexes. Nature 375 (1995) 148-151
48. Gros G., Ben-Sasson S.Z., Seder R., Finkelman F.D., and Paul W.E. Generation of interleukin 4 (IL-4)-producing cells in vivo and in vitro: IL-2 and IL-4 are required for in vitro generation of IL-4 producing cells. J Exp Med 172 (1990) 921-929
49. Grewal I.S., and Flavell R.A. The role of CD40 ligand in costimulation and T-cell activation. Innumol Rev 153 (1996) 85-106
50. Ridge J.P., Di Rosa F., and Matzinger P. A conditioned dendritic cell can be a temporal bridge between a CD4+ T-helper and a T-killer cell. Nature 393 (1998) 474-478
51. Russell S.M., and Liew F.Y. Cell cooperation in antibody responses to influenza virus. I. priming of helper t cells by internal components of virion. Eur J Immunol 10 (1980) 791-796
52. Fuchs E.J., and Matzinger P. B cells turn off virgin but not memory T cells. Science 258 (1992) 1156-1159
53. Gilbert K.M., and Weigle W.O. Tolerogenicity of resting and activated B cells. J Exp Med 179 (1994) 249-258
54. + T-cells specific for the protein NS4 of hepatitis C virus in patient with chronic hepatitis. J Exp Med 178 (1993) 17-26
55. Jacobson S., Richert J.R., Biddison W.E., Satinsk A., Hartzmann R.J., and McFarland H.F. Measles virus specific T4+ human cytotoxic T cell clones are restricted by class II HLA antigens. J Immunol 133 (1984) 754-757
56. Fleischer B., and Kreth H.W. Clonal expansion and functional analysis of virus-specific T lymphocytes from cerebrospinal fluid in measles encephalitis. Hum Immunol 7 (1983) 239-248
57. Franco A., Guidotti L.G., Hobbs M.V., Pasquetto V., and Chisari F.V. Pathogenetic effector function of CD4-positive T helper 1 cells in hepatitis B virus transgenic mice. J Immunol (1997) 2001-2008
58. Franco A., Paroli M., Testa U., et al. Transferrin receptor mediates uptake and presentation of hepatitis B envelope antigen by T lymphocytes. J Exp Med 175 (1992) 1195-1205
59. Wang C., and Splitter G.A. CD4(+) cytotoxic T-lymphocyte activity against macrophages pulsed with bovine herpesvirus 1 polypeptides. J Virol 72 (1998) 7040-7047
60. Valitutti S., Müller S., Dessing M., and Lanzavecchia A. Different responses are elicited in cytotoxic T lymphoytes by different levels of T cell receptor occupancy. J Exp Med 183 (1996) 1917-1921
61. Germain R.N. MHC-dependent antigen processing and peptide presentation: providing ligands for T lymphocyte activation. Cell 76 (1994) 287-299
62. Sijts A.J., and Pamer E.G. Enhanced intracellular dissociation of major histocompatibility complex class I-associated peptides: a mechanism for optimizing the spectrum of cell surface-presented cytotoxic T lymphocyte epitopes. J Exp Med 185 (1997) 1403-1411
63. Gilles P.N., Fey G., and Chisari F.V. Tumor necrosis factor-alpha negatively regulates hepatitis B virus gene expression in transgenic mice. J Virol 66 (1992) 3955-3960
64. Guidotti L.G., Guilhot S., and Chisari F.V. Interleukin 2 and interferon alph/beta downregulate hepatitis B virus gene expression in vivo by tumor necrosis factor dependent and independent pathways. J Virol 68 (1994) 1265-1270
65. Cocchi F., deVico A.L., Garzino-Demo A., Arya S.K., Gallo R.C., and Lusso P. Identification of Rantes, MIP-1 alpha and MIP-1 beta as the major HIV-suppressive factors produced by CD8+ T cells. Science 270 (1995) 1811-1815
66. Battegay M., Bachmann M.F., Burhkart C., et al. Antiviral immune responses of mice lacking MHC class II or its associated invariant chain. Cell Immunol 167 (1996) 115-121
67. Gallimore A., Hengartner H., and Zinkernagel R. Hierarchies of antigen-specific cytotoxic T-cell responses. Immunol Rev 164 (1998) 29-36
68. Alexander-Miller M.A., Leggatt G.R., Sarin A., and Berzofsky J.A. Role of antigen, CD8, and cytotoxic T lymphocyte (CTL) avidity in high dose antigen induction of apoptosis of effector CTL. J Exp Med 184 (1996) 485-492
69. Thomsen A.R., and Marker O. The complementary roles of cellular and humoral immunity in resistance to re-infection with LCM virus. Immunology 65 (1988) 9-15
70. Matloubian M., Concepcion R.J., and Ahmed R. CD4+ T cells are required to sustain CD8+ cytotoxic T-cell responses during chronic viral infection. J Virol 68 (1994) 8056-8063
71. Battegay M., Moskophidis D., Rahemtulla A., Hengartner H., Mak T.W., and Zinkernagel R.M. Enhanced establishment of a virus carrier state in adult CD4+ T-cell deficient mice. J Virol 68 (1994) 4700-4704
72. von Herrath M.G., and Oldstone M.B. Virus-induced autoimmune disease. Curr Opin Immunol 8 (1996) 878-885
73. von Herrath M.G., Dyrberg T., and Oldstone M.B. Oral insulin treatment suppresses virus-induced antigen-specific destruction of beta cells and prevents autoimmune diabetes in transgenic mice. J Clin Invest 98 (1996) 1324-1331
74. von Herrath M.G., Evans C.F., Horwitz M.S., and Oldstone M.B. Using transgenic mouse models to dissect the pathogenesis of virus- induced autoimmune disorders of the islets of Langerhans and the central nervous system. Immunol Rev 152 (1996) 111-143
75. Stohlman S.A., Bergmann C.C., Lin M.T., Cua D.J., and Hinton D.R. CTL effector function within the central nervous system requires CD4+ T cells. J Immunol 160 (1998) 2896-2904
76. Planz O., Seiler P., Hengartner H., and Zinkernagel R.M. Specific cytotoxic T cells eliminate B cells producing virus-neutralizing antibodies. Nature 382 (1996) 726-729
77. Battegay M., Moskophidis D., Waldner H., et al. Impairment and delay of neutralizing antiviral antibody responses by virus-specific cytotoxic T cells. J Immunol 151 (1993) 5408-5415
78. Salemi S., Caporossi A.P., Boffa L., Longobardi M.G., and Barnaba V. HIVgp120 activates autoreactive CD4-specific T cell responses by unveiling of hidden CD4 peptides during processing [see comments]. J Exp Med 181 (1995) 2253-2257
79. Ware R., Jiang H., Braunstein N., et al. Human CD8+ T lymphocyte clones specific for T cell receptor V beta families expressed on autologous CD4+ T cells. Immunity 2 (1995) 177-184
80. Giuberti T., Marin M.G., Ferrari C., et al. Hepatitis C virus viremia following clinical resolution of acute hepatitis C. J Hepatol 20 (1994) 666-671
81. Diepolder H.M., Zachoval R., Hoffmann R.M., et al. Possible mechanism involving T lymphocyte response to non-structural protein 3 in viral clearance in acute hepatitis C virus infection. Lancet 346 (1995) 1006-1007
82. Diepolder H.M., Gerlach J.-T., Zachoval R., et al. Immunodominant CD4+ T-cell epitope within nonstructural protein 3 in acute hepatitis C virus infection. J Virol 71 (1997) 6011-6019
83. Tsai S.-L., Liaw Y.-L., Chen M.-H., Huang C.-Y., and Kuo G.C. Detection of type 2-like T-helper cells in hepatitis C virus infection: implications for hepatitis C virus chronicity. Hepatology 25 (1997) 449-458
84. Cacciarelli T.V., Martinez O.M., Gish R.G., Villanueva J.C., and Krams S.M. Immunoregulatory cytokines in chronic hepatitis C virus infection: pre- and posttreatment with interferon alpha. Hepatology 24 (1996) 6-9
85. Diepolder H.M., Zachoval R., Hoffmann R.M., Jung M.C., Gerlach T., and Pape G.R. The role of hepatitis C virus specific CD4+ T lymphocytes in acute and chronic hepatitis C. J Mol Med 74 (1996) 583-588
86. Rehermann B., Ferrari C., Pasquinelli C., and Chisari F.V. The hepatitis B virus persists for decades after patients' recovery from acute viral hepatitis despite active maintenance of a cytotoxic T-lymphocyte response. Nat Med 2 (1996) 1104-1108
87. Katayama Y., Hotta H., Nishimura A., Tatsuno Y., and Homma M. Detection of measles virus nucleo-protein mRNA in autopsied brain tissues. J Gen Virol 76 (1995) 3201-3204
88. Kundig T.M., Bachmann M.F., Oehen S., et al. On the role of antigen in maintaining cytotoxic T-cell memory. Proc Natl Acad Sci U S A 93 (1996) 9716-9723
89. Belyakov I.M., Ahlers J.D., Brandwein B.Y., et al. The importance of local mucosal HIV-specific CD8(+) cytotoxic T lymphocytes for resistance to mucosal viral transmission in mice and enhancement of resistance by local administration of IL-12. J Clin Invest 102 (1998) 2072-2081
90. Selin L.K., Varga S.M., Wong I.C., and Welsh R.M. Protective heterologous antiviral immunity and enhanced immunopathogenesis mediated by memory T cell populations. J Exp Med 188 (1998) 1705-1715
91. Chang K.M., Gruener N.H., Southwood S., et al. Identification of HLA-A3 and -B7-restricted CTL response to hepatitis C virus in patients with acute and chronic hepatitis C. J Immunol 162 (1999) 1156-1164
92. Cooper S., Erickson A.L., Adams E.J., et al. Analysis of a successful immune response against hepatitis C virus. Immunity 10 (1999) 439-449
93. He X.S., Rehermann B., Lopez-Labrador F.X., 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 U S A 96 (1999) 5692-5697
94. Koziel M.J., Wong D.K.H., Dudley D., Houghton M., and Walker B.D. Hepatitis C Virus-specific cytolytic T lymphocyte and T helper cell responses in seronegative persons. J Infect Dis 176 (1997) 859-866
95. Scognamiglio P., Accapezzato D., Casciani A., et al. Presence of effector CD8+ T cells in hepatitis C virus-exposed healthy seronegative donors. J Immunol 162 (1999) 6681-6689
96. Bronowicki J.-P., Vetter D., Uhl G., et al. Lymphocyte reactivity to hepatitis C virus (HCV) antigens shows evidence for exposure in HCV-seronegative spouses of HCV-infected patients. J Infect Dis 176 (1997) 518-522
97. Clerici M., Giorgi J.V., Chou C.C., et al. Cell-mediated immune response to human immuno-deficiency virus (HIV) type 1 in seronegative homosexual men with recent sexual exposure to HIV-1. J Infect Dis 165 (1992) 1012-1019
98. Schupper H., Hayashi P., Scheffel J., et al. Peripheral blood mononuclear cell responses to recombinant hepatitis C virus antigens in patients with chronic hepatitis C. Hepatology 18 (1993) 1055-1060
99. Lechmann M., Ihlenfeldt H.G., Braunschweiger I., et al. T and B cell responses to different hepatitis C virus antigens in patients with chronic hepatitis C infection and in healthy anti-HCV blood donors withouth viremia. Hepatology 24 (1996) 790-795
100. Battegay M., Fikes J., Di Bisceglie A.M., et al. Patients with chronic hepatitis C have circulating cytotoxic T cells which recognize hepatitis C virus-encoded peptides binding to HLA-A2.1 molecules. J Virol 69 (1995) 2462-2470
101. Cerny A., McHutchison J.G., Pasquinelli C., et al. Cytotoxic T lymphocyte response to hepatitis C virus-derived peptides containing the HLA A2.1 binding motif. J Clin Invest 95 (1995) 521-530
102. Koziel M.J., and Walker B.D. Characteristics of the intrahepatic cytotoxic T lymphocyte response in chronic hepatitis C virus infection. Springer Semin Immunopathol 19 (1997) 69-83
103. Koziel M.J., Dudley D., Afdhal N., et al. Hepatitis C virus (HCV)-specific cytotoxic T lymphocytes recognize epitopes in the core and envelope proteins of HCV. J Virol 67 (1993) 7522-7532
104. Koziel M.J., Dudley D., Wong J.T., et al. Intrahepatic cytotoxic T lymphocytes specific for hepatitis C virus in persons with chronic hepatitis. J Immunol 149 (1992) 3339-3344
105. Erickson A.L., Houghton M., Choo Q.-L., et al. Hepatitis C virus-specific CTL responses in the liver of chimpanzees with acute and chronic hepatitis C. J Immunol 151 (1993) 4189-4199
106. Wentworth P.A., Sette A., Celis E., et al. Identification of A2-restricted HCV-specific CTL epitopes from highly conserved regions of the viral genome. Int Immunol 8 (1996) 651-659
107. Shirai M., Arichi T., Nishioka M., et al. CTL responses of HLA-A2.1-transgenic mice specific for hepatitis C viral peptides predict epitopes for CTL of humans carrying HLA-A2.1. J Immunol 154 (1995) 2733-2742
108. Ada G.L., and Jones P.D. The immune response to influenza infection. Curr Top Microbiol Immunol 128 (1986) 1-54
109. Doherty P.C., Allan W., Eichelberger M., and Carding S.R. Roles of alpha beta and gamma delta T cell subsets in viral immunity. Annu Rev Immunol 10 (1992) 123-151
110. McMichael A. Cytotoxic T lymphocytes specific for influenza virus. Curr Top Microbiol Immunol 189 (1994) 75-91
111. Dorrell L., Dong T., Ogg G.S., et al. Distinct recognition of non-clade B human immuno-deficiency virus type 1 epitopes by cytotoxic T lymphocytes generated from donors infected in Africa. J Virol 73 (1999) 1708-1714
112. Rowland-Jones S.L., Dong T., Fowke K.R., et al. Cytotoxic T cell responses to multiple conserved HIV epitopes in HIV - resistant prostitutes in Nairobi. J Clin Invest 102 (1998) 1758-1765
113. Bruna-Romero O., Lasarte J.J., Wilkinson G., et al. Induction of cytotoxic T-cell response against hepatitis C virus structural antigens using a defective recombinant adenovirus. Hepatology 25 (1997) 470-477
114. Del Guercio M.F., Sidney J., Hermanson G., et al. Binding of a peptide antigen to multiple HLA alleles allows definition of an A2-like supertype. J Immunol 154 (1995) 685-693
115. Sidney J., Del Guercio M.F., Southwood S., et al. Several HLA alleles share overlapping peptide specificities. J Immunol 154 (1995) 247-259
116. Sidney J., Grey H.M., Kubo R.T., and Sette A. Practical, biochemical and evolutionary implications of the discovery of HLA class I supermotifs. Immunol Today 17 (1996) 261-266
117. Sidney J., Grey H.M., Southwood S., et al. Definition of an HLA-A3-like supermotif demonstrates the overlapping peptide-binding repertoires of common HLA molecules. Hum Immunol 45 (1996) 79-93
118. Rehermann B., Chang K.M., McHutchison J.G., Kokka R., Houghton M., and Chisari F.V. 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 98 (1996) 1432-1440
119. Byrne J.A., and Oldstone M. Biolgoy of cloned cytotoxic T lymphocytes specific for lymphocytic choriomeningitis virus: clearance of virus in vivo. J Virol 51 (1984) 682-686
120. Hiroishi K., Kita H., Kojima M., et al. Cytotoxic T lymphocyte response and viral load in hepatitis C virus infection. Hepatology 25 (1997) 705-712
121. Wong D.K., Dudley D.D., Afdhal N.H., et al. Liver-derived CTL in hepatitis C virus infection: breadth and specificity of responses in a cohort of persons with chronic infection. J Immunol 160 (1998) 1479-1488
122. Nelson D.R., Marousis C.G., Davis G., et al. The role of hepatitis C virus-specific cytotoxic T lymphocytes in chronic hepatitis C. J Immunol 158 (1997) 1473-1481
123. Kashii Y., Shimizu Y., Nambu S., et al. Analysis of T-cell receptor V beta repertoire in liver-infiltrating lymphocytes in chronic hepatitis C. J Hepatol 26 (1997) 462-470
124. Rehermann B., Chang K.M., McHutchison J., et al. Differential cytotoxic T lymphocyte responsiveness to the hepatitis B and C viruses in chronically infected patients. J Virol 70 (1996) 7092-7102
125. Lanford R.E., Chavez D., Chisari F.V., and Sureau C. Lack of detection of negative-strand hepatitis C virus RNA in peripheral blood mononuclear cells and other extrahepatic tissues by the highly strand-specific rTth reverse transcriptase PCR. J Virol 69 (1995) 8079-8083
126. Terrault N.A., Dailey P.J., Ferrell L., et al. Hepatitis C virus: quantitation and distribution in liver. J Med Virol 51 (1997) 217-224
127. Sugano M., Hayashi Y., Yoon S., et al. Quantitation of hepatitis C viral RNA in liver and serum samples using competitive polymerase chain reaction. J Clin Pathol 48 (1995) 820-825
128. Lau G.K., Davis G.L., Wu S.P., Gish R.G., Balart L.A., and Lau J.Y. Hepatic expression of hepatitis C virus RNA in chronic hepatitis C: a study by in situ reverse-transcription polymerase chain reaction. Hepatology 23 (1996) 1318-1323
129. Agnello V., Abel G., Knight G.B., and Muchmore E. Detection of widespread hepatocyte infection in chronic hepatitis C. Hepatology 28 (1998) 573-584
130. Nouri-Aria K.T., Sallie R., Mizokami M., Portmann B.C., and Williams R. Intrahepatic expression of hepatitis C virus antigens in chronic liver disease. J Pathol 175 (1995) 77-83
131. Ballardini G., Groff P., Pontisso P., et al. Hepatitis C virus (HCV) genotype, tissue HCV antigens, hepatocellular expression of HLA-A, B, C, and intercellular adhesion-1 molecules. J Clin Invest 95 (1995) 2967-2975
132. Bach N., Thung S.N., and Schaffner F. The histological features of chronic hepatitis C and antoimmune chronic hepatitis: a comparative analysis. Hepatology 15 (1992) 572-577
133. Scheuer P.J., Ashrafzadeh P., Sherlock S., Brown D., and Dusheiko G.M. The pathology of hepatitis C. Hepatology 15 (1992) 567-571
134. Lefkowitch J.H., Schiff E.R., Davis G.L., et al. Pathological diagnosis of chronic hepatitis C: a multicenter comparative study with chronic hepatitis B. The Hepatitis Interventional Therapy Group. Gastroenterology 104 (1993) 595-603
135. Onji M., Kikuchi T., Kumon I., et al. Intrahepatic lymphocyte subpopulations and HLA class I antigen expression by hepatocytes in chronic hepatitis C. Hepatogastroenterology 39 (1992) 340-343
136. Gonzalez-Peralta R.P., Fang J.W.S., Davis G.L., et al. Immunopathobiology of chronic hepatitis C virus infection. Hepatology 20 (1994) 232A
137. Weiner A.J., Geysen H.M., Christopherson C., et al. Evidence for immune selection of hepatitis C virus (HCV) putative envelope glycoprotein variants: potential role in chronic HCV infection. Proc Natl Acad Sci U S A 89 (1992) 3468-3472
138. Yuk K., Shimizu M., Aoyama S., et al. Analysis of lymphocyte subsets in liver biopsy specimens with lymphoid follicle like structures. Acta Hepatol Jpn 27 (1986) 720-725
139. Hiramatsu N., Hayashi N., Katayama K., et al. Immunohistochemical detection of Fas antigen in liver tissue of patients with chronic hepatiits C. Hepatology 19 (1994) 1354-1359
140. Mosnier J.F., Scoaze J.Y., Marcellin P., Degott C., Benahmou J.P., and Feldmann G. Expression of cytokine-dependent immune adhesion molecules by hepatocytes. Gastroenterology 107 (1994) 1457-1468
141. Marrogi A.J., Cheles M.K., and Gerber M.A. Chronic hepatitis C. Analysis of host immune response by immunohistochemistry. Arch Pathol Lab Med 119 (1995) 232-237
142. Fukumoto T., Berg T., Ku Y., et al. Viral dynamics of hepatitis C early after orthotopic liver transplantation: evidence for rapid turnover of serum virions. Hepatology 24 (1996) 1351-1354
143. Guidotti L.G., and Chisari F.V. To kill or to cure: options in host defense against viral infection. Curr Opin Immunol 8 (1996) 478-483
144. Lohr H.F., Schlaak J.F., Kollmannsperger S., Dienes H.P., Meyer zum Buschenfelde K.H., and Gerken G. Liver-infiltrating and circulating CD4+ T cells in chronic hepatitis C: immunodominant epitopes, HLA-restriction and functional significance. Liver 16 (1996) 174-182
145. Bertoletti A., D'Elios M.M., Boni C., et al. Different cytokine profiles of intrahepatic T cells in chronic hepatitis B and hepatitis C virus infections. Gastroenterology 112 (1997) 193-199
146. Mita E., Hayashi N., Iio S., et al. Role of Fas ligand in apoptosis induced by hepatitis C virus infection. Biochem Biophys Res Commun 204 (1994) 468-474
147. Lohman B.L., Razvi E.S., and Welsh R.M. T-lymphocyte downregulation after acute viral infection is not dependent on CD95 (Fas) receptor-ligand interactions. J Virol 70 (1996) 8199-8203
148. Vassalli P. The pathophysiology of tumor necrosis factors. Annu Rev Immunol 10 (1992) 411-452
149. Koziel M.J., Dudley D., Afdhal N., et al. HLA class I-restricted cytotoxic T lymphocytes specific for hepatitis C virus. Identification of multiple epitopes and characterization of patterns of cytokine release. J Clin Invest 96 (1995) 2311-2321
150. Kinkhabwala M., Sehajpal P., Skolnik E., et al. A novel addition to the T cell repertory: cell surface expression of tumor necrosis factor/cachectin by activated normal human T cells. J Exp Med 171 (1990) 941-946
151. Ando K., Hiroishi K., Kaneko T., et al. Perforin, fas/fas ligand, and TNF-alpha pathways as specific and bystander killing mechanisms of hepatitis C virus-specific human CTL. J Immunol 158 (1997) 5283-5291
152. Cuturi M.C., Murphy M., Costa-Giomi M.P., Weinmann R., Perussia B., and Trinchieri G. Independent regulation of tumor necrosis factor and lymphotoxin production by human peripheral blood lymphocytes. J Exp Med 165 (1987) 1581-1594
153. Nuti S., Rosa D., Valiante N.M., et al. Dynamics of intra-hepatic lymphocytes in chronic hepatitis C: enrichment for Valpha24+ T cells and rapid elimination of effector cells by apoptosis. Eur J Immunol 28 (1998) 3448-3455
154. Zhang X., Brunner T., Carter L., et al. Unequal death in T helper cell (Th)1 and Th2 effectors: Th1, but not Th2, effectors undergo rapid Fas/FasL-mediated apoptosis. J Exp Med 185 (1997) 1837-1849
155. Neumann A.U., Lam N.P., Dahari H., et al. Hepatitis C viral dynamics in vivo and the antiviral efficacy of interferon-alpha therapy. Science 282 (1998) 103-107
156. Odeberg J., Yun Z., Sönnerborg A., Bjoro K., Uhlen M., and Lundeberg J. Variation of hepatitis C virus hypervariable region 1 in immunocompromised patients. J Infect Dis 175 (1997) 938-943
157. Major M.E., Mihalik K., Fernandez J., et al. Long-term follow-up of chimpanzees inoculated with the first infectious clone for hepatitis C virus. J Virol 73 (1999) 3317-3325
158. Bassett S.E., Thomas D.L., Brasky K.M., and Lanford R.E. Viral persistence, antibody to E1 and E2, and hypervariable region 1 sequence stability in hepatitis C virus-inoculated chimpanzees. J Virol 73 (1999) 1118-1126
159. Bertoletti A., Sette A., Chisari F.V., et al. Natural variants of cytotoxic epitopes are T-cell receptor antagonists for antiviral cytotoxic T cells. Nature 369 (1994) 407-410
160. Klenerman P., Rowland-Jones S., McAdams S., et al. Cytotoxic T-cell activity antagonized by naturally occurring HIV-1 Gag variants. Nature 369 (1994) 403-407
161. Niewiesk S., Daenke S., Parker C.E., et al. Naturally occurring variants of human T-cell leukemia virus type I Tax protein impair its recognition by cytotoxic T lymphocytes and the transactivation function of Tax. J Virol 69 (1995) 2649-2653
162. Borrow P., Wei X., Horwitz M.S., et al. Antiviral pressure exerted by HIV-1-specific cytotoxic T lymphocytes (CTLs) during primary infection demonstrated by rapid selection of CTL escape virus. Nat Med 3 (1997) 212-217
163. Goulder P.J., Phillips R.E., Colbert R.A., et al. Late escape from an immunodominant cytotoxic T-lymphocyte response associated with progression to AIDS. Nat Med 3 (1997) 212-217
164. Weiner A., Erickson A.L., Kansopon J., et al. Persistent hepatitis C virus infection in a chimpanzee is associated with emergence of a cytotoxic T lymphocyte escape variant. Proc Natl Acad Sci U S A 92 (1995) 2755-2759
165. Chang K.M., Rehermann B., McHutchison J.G., et al. Immunological significance of cytotoxic T lymphocyte epitope variants in patients chronically infected by the hepatitis C virus. J Clin Invest 100 (1997) 2376-2385
166. Kaneko T., Moriyama T., Udaka K., et al. Impaired induction of cytotoxic T lymphocytes by antagonism of a weak agonist borne by a variant hepatitis C virus epitope. Eur J Immunol 27 (1997) 1782-1787
167. Lanzavecchia A. Understanding the mechanisms of sustained signaling and T cell activation. J Exp Med 185 (1997) 1717-1719
168. Machold R.P., Wiertz E., Jones T.R., and Ploegh H.L. The HCMV gene products US11 and US2 differ in their ability to attack allelec forms of murine major histocompatibility complex (MHC) class I heavy chains. J Exp Med 185 (1997) 363-366
169. Large M.K., Kittlesen D.J., and Hahn Y.S. Suppression of host immune response by the core protein of hepatitis C virus: possible implications for hepatitis C virus persistence. J Immunol 162 (1999) 931-938