Immune outcomes in the liver: Is CD8 T cell fate determined by the environment?

Journal of Hepatology

Volumn 63, Issue 4, 2015, Pages 1005-1014

  Wong, Yik Chun ^a   Tay, Szun Szun ^a   McCaughan, Geoffrey W ^a   Bowen, David G ^a   Bertolino, Patrick ^a  

^a ROYAL PRINCE ALFRED HOSPITAL   (Australia)

Author keywords

Antigen load; CD4 T cell help; CD8 T cell exhaustion; Cytotoxic T cells; Immunity; Tolerance; Viral hepatitis

Indexed keywords

LIVER ANTIGEN;

ANTIGEN EXPRESSION; CD8+ T LYMPHOCYTE; CELL FATE; CELL SPECIFICITY; CELLULAR IMMUNITY; CROSS PRESENTATION; HEPATITIS; HUMAN; IMMUNE RESPONSE; IMMUNOLOGICAL TOLERANCE; LIVER; LYMPHOCYTE FUNCTION; LYMPHOID TISSUE; NONHUMAN; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; T CELL EXHAUSTION; T LYMPHOCYTE ACTIVATION; TUMOR MICROENVIRONMENT; ADAPTIVE IMMUNITY; ANIMAL; IMMUNOLOGY; LIVER CELL; LIVER DISEASE; PATHOLOGY;

ADAPTIVE IMMUNITY; ANIMALS; CD8-POSITIVE T-LYMPHOCYTES; HEPATOCYTES; HUMANS; IMMUNITY, CELLULAR; LIVER DISEASES;

EID: 84941938736     PISSN: 01688278     EISSN: 16000641     Source Type: Journal    
DOI: 10.1016/j.jhep.2015.05.033     Document Type: Review

References (150)

1. V. Benseler, G.W. McCaughan, H.J. Schlitt, G.A. Bishop, D.G. Bowen, and P. Bertolino The liver: a special case in transplantation tolerance Semin Liver Dis 27 2007 194 213
2. D.R. Triger, M.H. Cynamon, and R. Wright Studies on hepatic uptake of antigen. I. Comparison of inferior vena cava and portal vein routes of immunization Immunology 25 1973 941 950
3. F. Mingozzi, Y.-L. Liu, E. Dobrzynski, A. Kaufhold, J.H. Liu, Y. Wang, and et al. Induction of immune tolerance to coagulation factor IX antigen by in vivo hepatic gene transfer J Clin Invest 111 2003 1347 1356
4. + T cell effector mechanisms in resistance to infection Annu Rev Immunol 18 2000 275 308
5. + T cells mediate viral clearance and disease pathogenesis during acute hepatitis B virus infection J Virol 77 2003 68 76
6. D.G. Bowen, and C.M. Walker Adaptive immune responses in acute and chronic hepatitis C virus infection Nature 436 2005 946 952
7. C. Boni, P. Fisicaro, C. Valdatta, B. Amadei, P. Di Vincenzo, T. Giuberti, and et al. Characterization of hepatitis B virus (HBV)-specific T-cell dysfunction in chronic HBV infection J Virol 81 2007 4215 4225
8. + T cells specific for structural and nonstructural hepatitis B virus proteins in patients with chronic hepatitis B: implications for immunotherapy J Virol 78 2004 5707 5719
9. Y. Sobao, H. Tomiyama, K. Sugi, M. Tokunaga, T. Ueno, S. Saito, and et al. The role of hepatitis B virus-specific memory CD8 T cells in the control of viral replication J Hepatol 36 2002 105 115
10. A. Penna, M. Pilli, A. Zerbini, A. Orlandini, S. Mezzadri, L. Sacchelli, and et al. Dysfunction and functional restoration of HCV-specific CD8 responses in chronic hepatitis C virus infection Hepatology 45 2007 588 601
11. R.M. Zinkernagel, and P.C. Doherty Immunological surveillance against altered self components by sensitised T lymphocytes in lymphocytes choriomeningitis Nature 251 1974 547 548
12. A.R.M. Townsend, J. Rothbard, F.M. Gotch, G. Bahadur, D. Wraith, and A.J. McMichael The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptides Cell 44 1986 959 968
13. J.S. Blum, P.A. Wearsch, and P. Cresswell Pathways of antigen processing Annu Rev Immunol 31 2013 443 473
14. S. Nierkens, J. Tel, E. Janssen, and G.J. Adema Antigen cross-presentation by dendritic cell subsets: one general or all sergeants? Trends Immunol 34 2013 361 370
15. J.E. Smith-Garvin, G.A. Koretzky, and M.S. Jordan T cell activation Annu Rev Immunol 27 2009 591 619
16. + CTL activation by peptides and engineered influenza A viruses J Immunol 187 2011 5733 5744
17. D. Zehn, S.Y. Lee, and M.J. Bevan Complete but curtailed T-cell response to very low-affinity antigen Nature 458 2009 211 214
18. L. Chen, and D.B. Flies Molecular mechanisms of T cell co-stimulation and co-inhibition Nat Rev Immunol 13 2013 227 242
19. C. Reis e Sousa Dendritic cells in a mature age Nat Rev Immunol 6 2006 476 483
20. P.M. Odorizzi, and E.J. Wherry Inhibitory receptors on lymphocytes: insights from infections J Immunol 188 2012 2957 2965
21. + T cells and is overcome by IL-2 Eur J Immunol 32 2002 634 643
22. G.J. Freeman, A.J. Long, Y. Iwai, K. Bourque, T. Chernova, H. Nishimura, and et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation J Exp Med 192 2000 1027 1034
23. Y. Latchman, C.R. Wood, T. Chernova, D. Chaudhary, M. Borde, I. Chernova, and et al. PD-L2 is a second ligand for PD-1 and inhibits T cell activation Nat Immunol 2 2001 261 268
24. L.S.K. Walker, and D.M. Sansom The emerging role of CTLA4 as a cell-extrinsic regulator of T cell responses Nat Rev Immunol 11 2011 852 863
25. + T cells J Immunol 162 1999 3256 3262
26. J.M. Curtsinger, D.C. Lins, and M.F. Mescher Signal 3 determines tolerance versus full activation of baive CD8 T cells: dissociating proliferation and development of effector function J Exp Med 197 2003 1141 1151
27. J.M. Curtsinger, J.O. Valenzuela, P. Agarwal, D. Lins, and M.F. Mescher Cutting edge: type I IFNs provide a third signal to CD8 T cells to stimulate clonal expansion and differentiation J Immunol 174 2005 4465 4469
28. + T cell response during cross-priming J Immunol 176 2006 4682 4689
29. M.F. Bachmann, K. McKall-Faienza, R. Schmits, D. Bouchard, J. Beach, D.E. Speiser, and et al. Distinct roles for LFA-1 and CD28 during activation of naive T cells: adhesion versus costimulation Immunity 7 1997 549 557
30. C. Chirathaworn, J.E. Kohlmeier, S.A. Tibbetts, L.M. Rumsey, M.A. Chan, and S.H. Benedict Stimulation through intercellular adhesion molecule-1 provides a second signal for T cell activation J Immunol 168 2002 5530 5537
31. S.P. Schoenberger, R.E.M. Toes, E.I.H. van der Voort, R. Offringa, and C.J.M. Melief T-cell help for cytotoxic lymphocytes is mediated by CD40-CD40L interactions Nature 393 1998 480 483
32. S.R.M. Bennett, F.R. Carbone, F. Karamalis, R.A. Flavell, J.F.A.P. Miller, and W.R. Heath Help for cytotoxic-T-cell responses is mediated by CD40 signalling Nature 393 1998 478 480
33. + T cell immunity Nat Immunol 5 2004 1143 1148
34. + T-helper and a T-killer cell Nature 393 1998 474 478
35. M.A. Williams, and M.J. Bevan Effector and memory CTL differentiation Annu Rev Immunol 25 2007 171 192
36. J.C. Sun, and M.J. Bevan Defective CD8 T cell memory following acute infection without CD4 T cell help Science 300 2003 339 342
37. + T cells after acute infection Nat Immunol 5 2004 927 933
38. D.J. Shedlock, and H. Shen Requirement for CD4 T cell help in generating functional CD8 T cell memory Science 300 2003 337 339
39. H. von Boehmer Mechanisms of suppression by suppressor T cells Nat Immunol 6 2005 338 344
40. + T cells within the liver J Immunol 166 2001 5430 5438
41. + T cells to a transgenic autoantigen expressed in the liver does not require cross-presentation J Immunol 178 2007 6849 6860
42. + T cells activated locally within the transplanted liver J Exp Med 203 2006 437 447
43. + T cell activation by a non-self-antigen results in full functional differentiation J Immunol 177 2006 1689 1697
44. K. Derkow, C. Loddenkemper, J. Mintern, N. Kruse, K. Klugewitz, T. Berg, and et al. Differential priming of CD8 and CD4 T-cells in animal models of autoimmune hepatitis and cholangitis Hepatology 46 2007 1155 1165
45. S. Park, D. Murray, B. John, and I.N. Crispe Biology and significance of T-cell apoptosis in the liver Immunol Cell Biol 80 2002 74 83
46. P.F. Lalor, P. Shields, A.J. Grant, and D.H. Adams Recruitment of lymphocytes to the human liver Immunol Cell Biol 80 2002 52 64
47. P. Bertolino, G.W. McCaughan, and D.G. Bowen Role of primary intrahepatic T-cell activation in the 'liver tolerance effect' Immunol Cell Biol 80 2002 84 92
48. + T cells and successful immunotherapy against chronic viral liver infection Nat Immunol 14 2013 574 583
49. P. Bertolino, and D.G. Bowen Malaria and the liver: immunological hide-and-seek or subversion of immunity from within? Front Microbiol 6 2015 41
50. A.W. Thomson, and P.A. Knolle Antigen-presenting cell function in the tolerogenic liver environment Nat Rev Immunol 10 2010 753 766
51. I.N. Crispe Liver antigen-presenting cells J Hepatol 54 2011 357 365
52. A.W. Lohse, P.A. Knolle, K. Bilo, A. Uhrig, C. Waldmann, M. Ibe, and et al. Antigen-presenting function and B7 expression of murine sinusoidal endothelial cells and Kupffer cells Gastroenterology 110 1996 1175 1181
53. + T lymphocytes but fail to promote survival Eur J Immunol 28 1998 221 236
54. S.C. Katz, V.G. Pillarisetty, J.I. Bleier, A.B. Shah, and R.P. DeMatteo Liver sinusoidal endothelial cells are insufficient to activate T cells J Immunol 173 2004 230 235
55. M.-C. Yu, C.-H. Chen, X. Liang, L. Wang, C.R. Gandhi, J.J. Fung, and et al. Inhibition of T-cell responses by hepatic stellate cells via B7-H1-mediated T-cell apoptosis in mice Hepatology 40 2004 1312 1321
56. L.E. Holz, V. Benseler, D.G. Bowen, P. Bouillet, A. Strasser, L. O'Reilly, and et al. Intrahepatic murine CD8 T-cell activation associates with a distinct phenotype leading to Bim-dependent death Gastroenterology 135 2008 989 997
57. Y. Iwai, S. Terawaki, M. Ikegawa, T. Okazaki, and T. Honjo PD-1 inhibits antiviral immunity at the effector phase in the liver J Exp Med 198 2003 39 50
58. M. Mühlbauer, M. Fleck, C. Schütz, T. Weiss, M. Froh, C. Blank, and et al. PD-L1 is induced in hepatocytes by viral infection and by interferon-α and -γ and mediates T cell apoptosis J Hepatol 45 2006 520 528
59. + T lymphocytes in the liver J Immunol 178 2007 2714 2720
60. + T cell tolerance Hepatology 47 2008 296 305
61. A. Schurich, M. Berg, D. Stabenow, J. Böttcher, M. Kern, H.-J. Schild, and et al. Dynamic regulation of CD8 T cell tolerance induction by liver sinusoidal endothelial cells J Immunol 184 2010 4107 4114
62. D.M. Bissell, S.S. Wang, W.R. Jarnagin, and F.J. Roll Cell-specific expression of transforming growth factor-β in rat liver. Evidence for autocrine regulation of hepatocyte proliferation J Clin Invest 96 1995 447 455
63. P.J. De Bleser, T. Niki, V. Rogiers, and A. Geerts Transforming growth factor-β gene expression in normal and fibrotic rat liver J Hepatol 26 1997 886 893
64. P.A. Knolle, A. Uhrig, U. Protzer, M. Trippler, R. Duchmann, K.-H. Meyer zum Büschenfelde, and et al. Interleukin-10 expression is autoregulated at the transcriptional level in human and murine kupffer cells Hepatology 27 1998 93 99
65. Q. You, L. Cheng, R.M. Kedl, and C. Ju Mechanism of T cell tolerance induction by murine hepatic Kupffer cells Hepatology 48 2008 978 990
66. + Tregs by liver sinusoidal endothelial cells J Hepatol 61 2014 594 599
67. A. Warren, D.G. Le Couteur, R. Fraser, D.G. Bowen, G.W. McCaughan, and P. Bertolino T lymphocytes interact with hepatocytes through fenestrations in murine liver sinusoidal endothelial cells Hepatology 44 2006 1182 1190
68. M. Chen, P. Tabaczewski, S.M. Truscott, L. Van Kaer, and I. Stroynowski Hepatocytes express abundant surface class I MHC and efficiently use transporter associated with antigen processing, tapasin, and low molecular weight polypeptide proteasome subunit components of antigen processing and presentation pathway J Immunol 175 2005 1047 1055
69. G.L. Bumgardner, A.J. Matas, S. Chen, D. Cahill, T.R. Cunningham, W.D. Payne, and et al. Comparison of in vivo and in vitro immune response to purified hepatocytes Transplantation 49 1990 429 435
70. G.L. Bumgardner, J. Li, S. Apte, M. Heininger, and W.L. Frankel Effect of tumor necrosis factor α and intercellular adhesion molecule-1 expression on immunogenicity of murine liver cells in mice Hepatology 28 1998 466 474
71. b in the liver Eur J Immunol 25 1995 1932 1942
72. D.G. Bowen, M. Zen, L. Holz, T. Davis, G.W. McCaughan, and P. Bertolino The site of primary T cell activation is a determinant of the balance between intrahepatic tolerance and immunity J Clin Invest 114 2004 701 712
73. D. Voehringer, C. Blaser, A.B. Grawitz, F.V. Chisari, K. Buerki, and H. Pircher Break of T cell ignorance to a viral antigen in the liver induces hepatitis J Immunol 165 2000 2415 2422
74. M.A.A. Claassen, R.J. de Knegt, H.W. Tilanus, H.L.A. Janssen, and A. Boonstra Abundant numbers of regulatory T cells localize to the liver of chronic hepatitis C infected patients and limit the extent of fibrosis J Hepatol 52 2010 315 321
75. + T cells from PD-1-mediated exhaustion PLoS Pathog 9 2013 e1003490
76. D. Wohlleber, H. Kashkar, K. Gärtner, K. Frings Marianne, M. Odenthal, S. Hegenbarth, and et al. TNF-induced target cell killing by CTL activated through cross-presentation Cell Rep 2 2012 478 487
77. + T cells results in antigen-specific T-cell tolerance Nat Med 6 2000 1348 1354
78. B. Höchst, F.A. Schildberg, J. Böttcher, C. Metzger, S. Huss, A. Türler, and et al. Liver sinusoidal endothelial cells contribute to CD8 T cell tolerance toward circulating carcinoembryonic antigen in mice Hepatology 56 2012 1924 1933
79. M.D. Witmer-Pack, M.T. Crowley, K. Inaba, and R.M. Steinman Macrophages, but not dendritic cells, accumulate colloidal carbon following administration in situ J Cell Sci 105 1993 965 973
80. J. Woo, L. Lu, A.S. Rao, Y. Li, V. Subbotin, T.E. Starzl, and et al. Isolation, phenotype, and allostimulatory activity of mouse liver dendritic cells Transplantation 58 1994 484 491
81. + lymphoid-related dendritic cells J Immunol 165 2000 795 803
82. V. Benseler, A. Warren, M. Vo, L.E. Holz, S.S. Tay, D.G. Le Couteur, and et al. Hepatocyte entry leads to degradation of autoreactive CD8 T cells Proc Natl Acad Sci U S A 108 2011 16735 16740
83. A. Tsukahara, S. Seki, T. Iiai, T. Moroda, H. Watanabe, S. Suzuki, and et al. Mouse liver T cells: their change with aging and in comparison with peripheral T cells Hepatology 26 1997 301 309
84. G. Eberl, R. Lees, S.T. Smiley, M. Taniguchi, M.J. Grusby, and H.R. MacDonald Tissue-specific segregation of CD1d-dependent and CD1d-independent NK T cells J Immunol 162 1999 6410 6419
85. + regulatory T cells actively influence the antiviral immune response and disease progression in patients with hepatitis B J Immunol 177 2006 739 747
86. Y.H. Oo, C.J. Weston, P.F. Lalor, S.M. Curbishley, D.R. Withers, G.M. Reynolds, and et al. Distinct roles for CCR4 and CXCR3 in the recruitment and positioning of regulatory T cells in the inflamed human liver J Immunol 184 2010 2886 2898
87. K.-H. Sonoda, D.E. Faunce, M. Taniguchi, M. Exley, S. Balk, and J. Stein-Streilein NK T cell-derived IL-10 is essential for the differentiation of antigen-specific T regulatory cells in systemic tolerance J Immunol 166 2001 42 50
88. + T cells with PD-1-dependent regulatory activities Immunology 120 2007 73 82
89. + regulatory T cells protect the liver from immune damage and compromise virus control during acute experimental hepatitis B virus infection in mice Hepatology 56 2012 873 883
90. + T lymphocyte responses are induced during acute hepatitis C virus infection but are not sustained Eur J Immunol 30 2000 2479 2487
91. F. Lechner, D.K.H. Wong, P.R. Dunbar, R. Chapman, R.T. Chung, P. Dohrenwend, and et al. Analysis of successful immune responses in persons infected with hepatitis C virus J Exp Med 191 2000 1499 1512
92. G.J.M. Webster, S. Reignat, M.K. Maini, S.A. Whalley, G.S. Ogg, A. King, and et al. Incubation phase of acute hepatitis B in man: dynamic of cellular immune mechanisms Hepatology 32 2000 1117 1124
93. R. Thimme, D. Oldach, K.-M. Chang, C. Steiger, S.C. Ray, and F.V. Chisari Determinants of viral clearance and persistence during acute hepatitis C virus infection J Exp Med 194 2001 1395 1406
94. + cells in liver damage and viral control during persistent hepatitis B virus infection J Exp Med 191 2000 1269 1280
95. K.S. Lang, P. Georgiev, M. Recher, A.A. Navarini, A. Bergthaler, M. Heikenwalder, and et al. Immunoprivileged status of the liver is controlled by Toll-like receptor 3 signaling J Clin Invest 116 2006 2456 2463
96. K. Béland, P. Lapierre, I. Djilali-Saiah, and F. Alvarez Liver restores immune homeostasis after local inflammation despite the presence of autoreactive T cells PLoS One 7 2012 e48192
97. E.J. Hennessy, A.E. Parker, and L.A.J. O'Neill Targeting Toll-like receptors: emerging therapeutics? Nat Rev Drug Discov 9 2010 293 307
98. + T cells by adeno-associated virus-transduced hepatocytes Hepatology 52 2010 1068 1077
99. + T-cell immunity to adeno-associated virus can result in prolonged liver injury and fibrogenesis Am J Pathol 179 2011 2370 2381
100. S.S. Tay, Y.C. Wong, D.M. McDonald, N.A.W. Wood, B. Roediger, F. Sierro, and et al. Antigen expression level threshold tunes the fate of CD8 T cells during primary hepatic immune responses Proc Natl Acad Sci U S A 111 2014 E2540 E2549
101. M. Matloubian, S.R. Kolhekar, T. Somasundaram, and R. Ahmed Molecular determinants of macrophage tropism and viral persistence: importance of single amino acid changes in the polymerase and glycoprotein of lymphocytic choriomeningitis virus J Virol 67 1993 7340 7349
102. P. Borrow, C.F. Evans, and M.B. Oldstone Virus-induced immunosuppression: immune system-mediated destruction of virus-infected dendritic cells results in generalized immune suppression J Virol 69 1995 1059 1070
103. E.J. Wherry, J.N. Blattman, K. Murali-Krishna, R. van der Most, and R. Ahmed Viral persistence alters CD8 T-cell immunodominance and tissue distribution and results in distinct stages of functional impairment J Virol 77 2003 4911 4927
104. D. Moskophidis, F. Lechner, H. Pircher, and R.M. Zinkernagel Virus persistence in acutely infected immunocompetent mice by exhaustion of antiviral cytotoxic effector T cells Nature 362 1993 758 761
105. D.L. Barber, E.J. Wherry, D. Masopust, B. Zhu, J.P. Allison, A.H. Sharpe, and et al. Restoring function in exhausted CD8 T cells during chronic viral infection Nature 439 2006 682 687
106. H.-T. Jin, A.C. Anderson, W.G. Tan, E.E. West, S.-J. Ha, K. Araki, and et al. Cooperation of Tim-3 and PD-1 in CD8 T-cell exhaustion during chronic viral infection Proc Natl Acad Sci U S A 107 2010 14733 14738
107. + T cell exhaustion by multiple inhibitory receptors during chronic viral infection Nat Immunol 10 2009 29 37
108. D.G. Brooks, M.J. Trifilo, K.H. Edelmann, L. Teyton, D.B. McGavern, and M.B.A. Oldstone Interleukin-10 determines viral clearance or persistence in vivo Nat Med 12 2006 1301 1309
109. M. Ejrnaes, C.M. Filippi, M.M. Martinic, E.M. Ling, L.M. Togher, S. Crotty, and et al. Resolution of a chronic viral infection after interleukin-10 receptor blockade J Exp Med 203 2006 2461 2472
110. P. Penaloza-MacMaster, A.O. Kamphorst, A. Wieland, K. Araki, S.S. Iyer, E.E. West, and et al. Interplay between regulatory T cells and PD-1 in modulating T cell exhaustion and viral control during chronic LCMV infection J Exp Med 211 2014 1905 1918
111. I. Schmitz, C. Schneider, A. Fröhlich, H. Frebel, D. Christ, W.J. Leonard, and et al. IL-21 restricts virus-driven Treg cell expansion in chronic LCMV infection PLoS Pathog 9 2013 e1003362
112. S.N. Waggoner, M. Cornberg, L.K. Selin, and R.M. Welsh Natural killer cells act as rheostats modulating antiviral T cells Nature 481 2012 394 398
113. + T-cell immunity Proc Natl Acad Sci U S A 109 2012 1210 1215
114. K.D. Cook, and J.K. Whitmire The depletion of NK cells prevents T cell exhaustion to efficiently control disseminating virus infection J Immunol 190 2013 641 649
115. J. Chen, X.-M. Wang, X.-J. Wu, Y. Wang, H. Zhao, B. Shen, and et al. Intrahepatic levels of PD-1/PD-L correlate with liver inflammation in chronic hepatitis B Inflamm Res 60 2011 47 53
116. J.A. Mengshol, L. Golden-Mason, T. Arikawa, M. Smith, T. Niki, R. McWilliams, and et al. A Crucial role for Kupffer cell-derived galectin-9 in regulation of T cell immunity in hepatitis C infection PLoS One 5 2010 e9504
117. J.K. Flynn, G.J. Dore, M. Hellard, B. Yeung, W.D. Rawlinson, P.A. White, and et al. Early IL-10 predominant responses are associated with progression to chronic hepatitis C virus infection in injecting drug users J Viral Hepat 18 2011 549 561
118. J. Li, W. Wu, G. Peng, F. Chen, M. Bai, M. Zheng, and et al. HBcAg induces interleukin-10 production, inhibiting HBcAg-specific Th17 responses in chronic hepatitis B patients Immunol Cell Biol 88 2010 834 841
119. J.N. Stoop, R.G. van der Molen, C.C. Baan, L.J.W. van der Laan, E.J. Kuipers, J.G. Kusters, and et al. Regulatory T cells contribute to the impaired immune response in patients with chronic hepatitis B virus infection Hepatology 41 2005 771 778
120. D. Peppa, U.S. Gill, G. Reynolds, N.J.W. Easom, L.J. Pallett, A. Schurich, and et al. Up-regulation of a death receptor renders antiviral T cells susceptible to NK cell-mediated deletion J Exp Med 210 2013 99 114
121. S.N. Mueller, and R. Ahmed High antigen levels are the cause of T cell exhaustion during chronic viral infection Proc Natl Acad Sci U S A 106 2009 8623 8628
122. + T-cell exhaustion during chronic viral infection irrespective of the type of antigen presenting cell Eur J Immunol 42 2012 2290 2304
123. + T cell exhaustion J Immunol 182 2009 6697 6708
124. A.-K. Zaiss, Q. Liu, G.P. Bowen, N.C.W. Wong, J.S. Bartlett, and D.A. Muruve Differential activation of innate immune responses by adenovirus and adeno-associated virus vectors J Virol 76 2002 4580 4590
125. E.C. Cunningham, S.S. Tay, C. Wang, M. Rtshiladze, Z.Z. Wang, C. McGuffog, and et al. Gene therapy for tolerance: high-level expression of donor major histocompatibility complex in the liver overcomes naive and memory alloresponses to skin grafts Transplantation 95 2013 70 77
126. + T cell effector functions after antigen recognition in the liver Immunity 23 2005 53 63
127. S. Prato, Y. Zhan, J.D. Mintern, and J.A. Villadangos Rapid deletion and inactivation of CTLs upon recognition of a number of target cells over a critical threshold J Immunol 191 2013 3534 3544
128. M.J. Fuller, B. Callendret, B. Zhu, G.J. Freeman, D.L. Hasselschwert, W. Satterfield, and et al. Immunotherapy of chronic hepatitis C virus infection with antibodies against programmed cell death-1 (PD-1) Proc Natl Acad Sci U S A 110 2013 15001 15006
129. A. Das, G. Ellis, C. Pallant, A.R. Lopes, P. Khanna, D. Peppa, and et al. IL-10-producing regulatory B cells in the pathogenesis of chronic hepatitis B virus infection J Immunol 189 2012 3925 3935
130. A. Schurich, P. Khanna, A.R. Lopes, K.J. Han, D. Peppa, L. Micco, and et al. Role of the coinhibitory receptor cytotoxic T lymphocyte antigen-4 on apoptosis-prone CD8 T cells in persistent hepatitis B virus infection Hepatology 53 2011 1494 1503
131. P. Fisicaro, C. Valdatta, M. Massari, E. Loggi, L. Ravanetti, S. Urbani, and et al. Combined blockade of programmed death-1 and activation of CD137 increase responses of human liver T cells against HBV, but not HCV Gastroenterology 143 2012 1576 1585
132. N. Nakamoto, H. Cho, A. Shaked, K. Olthoff, M.E. Valiga, M. Kaminski, and et al. Synergistic reversal of intrahepatic HCV-specific CD8 T cell exhaustion by combined PD-1/CTLA-4 blockade PLoS Pathog 5 2009 e1000313
133. N. Nakamoto, D.E. Kaplan, J. Coleclough, Y. Li, M.E. Valiga, M. Kaminski, and et al. Functional restoration of HCV-specific CD8 T cells by PD-1 blockade is defined by PD-1 expression and compartmentalization Gastroenterology 134 2008 1927 1937
134. S. Owusu Sekyere, P.V. Suneetha, A.R.M. Kraft, S. Zhang, J. Dietz, C. Sarrazin, and et al. A heterogeneous hierarchy of co-regulatory receptors regulates exhaustion of HCV-specific CD8 T cells in patients with chronic hepatitis C J Hepatol 62 2015 31 40
135. S.D. Blackburn, H. Shin, G.J. Freeman, and E.J. Wherry Selective expansion of a subset of exhausted CD8 T cells by αPD-L1 blockade Proc Natl Acad Sci U S A 105 2008 15016 15021
136. V. Velu, K. Titanji, B. Zhu, S. Husain, A. Pladevega, L. Lai, and et al. Enhancing SIV-specific immunity in vivo by PD-1 blockade Nature 458 2009 206 210
137. D. Gardiner, J. Lalezari, E. Lawitz, M. DiMicco, R. Ghalib, K.R. Reddy, and et al. A randomized, double-blind, placebo-controlled assessment of BMS-936558, a fully human monoclonal antibody to programmed death-1 (PD-1), in patients with chronic hepatitis C virus infection PLoS One 8 2013 e63818
138. A. Schurich, L.J. Pallett, M. Lubowiecki, H.D. Singh, U.S. Gill, P.T. Kennedy, and et al. The third signal cytokine IL-12 rescues the anti-viral function of exhausted HBV-specific CD8 T cells PLoS Pathog 9 2013 e1003208
139. + T cells in hepatitis B and C are characterized by a lack of antigen-specific T-bet induction J Exp Med 211 2014 2047 2059
140. + T-cell-deficient mice J Virol 68 1994 4700 4704
141. + cytotoxic T-cell responses during chronic viral infection J Virol 68 1994 8056 8063
142. A.J. Zajac, J.N. Blattman, K. Murali-Krishna, D.J.D. Sourdive, M. Suresh, J.D. Altman, and et al. Viral immune evasion due to persistence of activated T cells without effector function J Exp Med 188 1998 2205 2213
143. R.D. Aubert, A.O. Kamphorst, S. Sarkar, V. Vezys, S.-J. Ha, D.L. Barber, and et al. Antigen-specific CD4 T-cell help rescues exhausted CD8 T cells during chronic viral infection Proc Natl Acad Sci U S A 108 2011 21182 21187
144. H. Elsaesser, K. Sauer, and D.G. Brooks IL-21 is required to control chronic viral infection Science 324 2009 1569 1572
145. A. Fröhlich, J. Kisielow, I. Schmitz, S. Freigang, A.T. Shamshiev, J. Weber, and et al. IL-21R on T cells Is critical for sustained functionality and control of chronic viral infection Science 324 2009 1576 1580
146. J.S. Yi, M. Du, and A.J. Zajac A vital role for interleukin-21 in the control of a chronic viral infection Science 324 2009 1572 1576
147. K. Derkow, A. Müller, I. Eickmeier, D. Seidel, M.V. Rust Moreira, N. Kruse, and et al. Failure of CD4 T-cells to respond to liver-derived antigen and to provide help to CD8 T-cells PLoS One 6 2011 e21847
148. + T cells by liver-resident phagocytic cells J Immunol 193 2014 2087 2095
149. A. Grakoui, N.H. Shoukry, D.J. Woollard, J.-H. Han, H.L. Hanson, J. Ghrayeb, and et al. HCV persistence and immune evasion in the absence of memory T cell help Science 302 2003 659 662
150. S. Asabe, S.F. Wieland, P.K. Chattopadhyay, M. Roederer, R.E. Engle, R.H. Purcell, and et al. The size of the viral inoculum contributes to the outcome of hepatitis B virus infection J Virol 83 2009 9652 9662