HBV-specific adaptive immunity

Viruses

Volumn 1, Issue 2, 2009, Pages 91-103

  Bertoletti, Antonio ^a,b,c   Tan, Anthony T ^a   Gehring, Adam J ^a  

^a AGENCY FOR SCIENCE   (Singapore)

^b AGENCY FOR SCIENCE   (Singapore)

^c DUKE NUS MEDICAL SCHOOL   (Singapore)

Author keywords

B cells; HBV; T cells

Indexed keywords

EID: 80054037525     PISSN: 19994915     EISSN: None     Source Type: Journal    
DOI: 10.3390/v1020091     Document Type: Review

References (80)

1. Chisari, F. Cytotoxic T cells and viral hepatitis. J. Clin. Invest. 1997, 99, 1472-1477.
2. Guidotti, L.; Chisari, F. To kill or to cure: options in host defense against viral infection. Current Opin. Immunol. 1996, 8, 478-483.
3. Alberti, A.; Diana, S.; Sculard, G.H.; Eddleston, A.L.; Williams, R. Detection of a new antibody system reacting with Dane particles in hepatitis B virus infection. Br. Med. J. 1978, 2, 1056-1058.
4. Grady, G.F.; Lee, V.A.; Prince, A.M.; Gitnick, G.L.; Fawaz, K.A.; Vyas, G.N.; Levitt, M.D.; Senior, J.R.; Galambos, J.T.; Bynum, T.E.; Singleton, J.W.; Clowdus, B.F.; Akdamar, K.; Aach, R.D.; Winkelman, E.I.; Schiff, G.M.; Hersh, T. Hepatitis B immune globulin for accidental exposures among medical personnel: final report of a multicenter controlled trial. J. Infect. Dis. 1978, 138, 625-638.
5. Chisari, F.; Ferrari, C. Hepatitis B virus immunopathogenesis. Ann. Rev. Immunol. 1995, 13, 29-60.
6. Bertoletti, A.; Gehring, A.J. The immune response during hepatitis B virus infection. J Gen Virol 2006, 87, 1439-1449.
7. Fisicaro, P.; Valdatta, C.; Boni, C.; Massari, M.; Mori, C.; Zerbini, A.; Orlandini, A.; Sacchelli, L.; Missale, G.; Ferrari, C. Early kinetics of innate and adaptive immune responses during hepatitis B virus infection. Gut 2009, 58, 974-982.
8. Wieland, S.F.; Chisari, F.V. Stealth and cunning: hepatitis B and hepatitis C viruses. J. Virol. 2005, 79, 9369-9380.
9. Ferrari, C.; Penna, A.; Bertoletti, A.; Valli, A.; Degli Antoni, A.; Giuberti, T.; Cavalli, A.; Petit, M.A.; Fiaccadori, F. Cellular immune response to hepatitis B virus encoded antigens in acute and chronic hepatitis B virus infection. J. Immunol. 1990, 145, 3442-3449.
10. Jung, M.; Spengler, U.; Schraut, W.; Hoffman, R.; Zachoval, R.; Eisemburg, J.; Eichenlaub, D.; Riethmuller, G.; Paumgartner, G.; Ziegler-Heitbrock, H.W.L.; Pape, G.R. Hepatitis B virus antigen-specific T-cell activation in patients with acute and chronic hepatitis B. J. Hepatol. 1991, 13, 310-317.
11. Penna, A.; Artini, M.; Cavalli, A.; Levrero, M.; Bertoletti, A.; Pilli, M.; Chisari, F.V.; Rehermann, B.; Del Prete, G.; Fiaccadori, F.; Ferrari, C. Long-lasting memory T cell responses following selflimited acute hepatitis B. J. Clin. Invest. 1996, 98, 1185-1194.
12. Penna, A.; Del Prete, G.; Cavalli, A.; Bertoletti, A.; D'Elios, M.M.; Sorrentino, R.; D'Amato, M.; Boni, C.; Pilli, M.; Fiaccadori, F.; Ferrari, C. Predominant T-helper 1 cytokine profile of hepatitis B virus nucleocapsid-specific T cells in acute self-limited hepatitis B. Hepatology 1997, 25, 1022-1027.
13. Rehermann, B.; Fowler, P.; Sidney, J.; Person, J.; Redeker, A.; Brown, M.; Moss, B.; Sette, A.; Chisari, F.V. The cytotoxic T lymphocyte response to multiple hepatitis B virus polymerase epitopes during and after acute viral hepatitis. J. Exp. Med. 1995, 181, 1047-1058.
14. Penna, A.; Chisari, F.V.; Bertoletti, A.; Missale, G.; Fowler, P.; Giuberti, T.; Fiaccadori, F.; Ferrari, C. Cytotoxic T lymphocytes recognize an HLA-A2-restricted epitope within the hepatitis B virus nucleocapsid antigen. J. Exp. Med. 1991, 174, 1565-1570.
15. Jung, M.; Hartmann, B.; Gerlach, J.; Diepolder, H.; Gruber, R.; Schraut, W.; Gruner, N.; Zachoval, R.; Hoffmann, R.; Santantonio, T.; Pape, G. Virus-specific lymphokine production differs quantitatively but not qualitatively in acute and chronic hepatitis B infection. Virology 1999, 261, 165-172.
16. Maini, M.K.; Boni, C.; Ogg, G.S.; King, A.S.; Reignat, S.; Lee, C.K.; Larrubia, J.R.; Webster, G. J.M.; McMichael, A.J.; Ferrari, C.; Williams, R.; Vergani, D.; Bertoletti, A. Direct ex vivo analysis of hepatitis B virus-specific CD8+ T cells associated with the control of infection. Gastroenterology 1999, 117, 1386-1396.
17. Sobao, Y.; Tomiyama, H.; Sugi, K.; Tokunaga, M.; Ueno, T.; Saito, S.; Fujiyama, S.; Morimoto, M.; Tanaka, K.; Takiguchi, M. The role of hepatitis B virus-specific memory CD8 T cells in the control of viral replication. J. Hepatol. 2002, 36, 105-115.
18. Webster, G.J.; Reignat, S.; Brown, D.; Ogg, G.S.; Jones, L.; Seneviratne, S.L.; Williams, R.; Dusheiko, G.; Bertoletti, A. Longitudinal analysis of CD8+ T cells specific for structural and nonstructural hepatitis B virus proteins in patients with chronic hepatitis B: implications for immunotherapy. J. Virol. 2004, 78, 5707-5719.
19. Chang, J.J.; Wightman, F.; Bartholomeusz, A.; Ayres, A.; Kent, S.J.; Sasadeusz, J.; Lewin, S.R. Reduced hepatitis B virus (HBV)-specific CD4+ T-cell responses in human immunodeficiency virus type 1-HBV-coinfected individuals receiving HBV-active antiretroviral therapy. J. Virol. 2005, 79, 3038-3051.
20. Boni, C.; Fisicaro, P.; Valdatta, C.; Amadei, B.; Di Vincenzo, P.; Giuberti, T.; Laccabue, D.; Zerbini, A.; Cavalli, A.; Missale, G.; Bertoletti, A.; Ferrari, C. Characterization of hepatitis B virus (HBV)-specific T-cell dysfunction in chronic HBV infection. J. Virol. 2007, 81, 4215-4225.
21. Menne, S.; Roneker, C.A.; Roggendorf, M.; Gerin, J. L.; Cote, P.J.; Tennant, B.C. Deficiencies in the acute-phase cell-mediated immune response to viral antigens are associated with development of chronic woodchuck hepatitis virus infection following neonatal inoculation. J. Virol. 2002, 76, 1769-1780.
22. Webster, G.; Reignat, S.; Maini, M.; Whalley, S.; Ogg, G.; King, A.; Brown, D.; Amlot, P.; Williams, R.; Vergani, D.; Dusheiko, G.; Bertoletti, A. Incubation phase of acute Hepatitis B in man: dynamic of cellular immune mechanism. Hepatology 2000, 32, 1117-1124.
23. Urbani, S.; Boni, C.; Amadei, B.; Fisicaro, P.; Cerioni, S.; Valli, M. A.; Missale, G.; Ferrari, C. Acute phase HBV-specific T cell responses associated with HBV persistence after HBV/HCV coinfection. Hepatology 2005, 41, 826-831.
24. Boettler, T.; Panther, E.; Bengsch, B.; Nazarova, N.; Spangenberg, H. C.; Blum, H.E.; Thimme, R. Expression of the interleukin-7 receptor alpha chain (CD127) on virus-specific CD8+ T cells identifies functionally and phenotypically defined memory T cells during acute resolving hepatitis B virus infection. J. Virol. 2006, 80, 3532-3540.
25. Zhang, Z.; Jin, B.; Zhang, J.Y.; Xu, B.; Wang, H.; Shi, M.; Wherry, E.J.; Lau, G.K.; Wang, F.S. Dynamic decrease in PD-1 expression correlates with HBV-specific memory CD8 T-cell development in acute self-limited hepatitis B patients. J. Hepatol. 2009, 50, 1163-1173.
26. Thimme, R.; Wieland, S.; Steiger, C.; Ghrayeb, J.; Reimann, K.A.; Purcell, R.H.; Chisari, F.V. CD8(+) T cells mediate viral clearance and disease pathogenesis during acute hepatitis B virus infection. J. Virol. 2003, 77, 68-76.
27. Ilan, Y.; Nagler, A.; Adler, R.; Tur-Kaspa, R.; Slavin, S.; Shouval, D. Ablation of persistent hepatitis B by bone marrow transplantation from a hepatitis B-immune donor. Gastroenterology 1993, 104, 1818-1821.
28. Lau, G.K.; Lok, A.S.; Liang, R.H.; Lai, C.L.; Chiu, E.K.; Lau, Y.L.; Lam, S.K. Clearance of hepatitis B surface antigen after bone marrow transplantation: role of adoptive immunity transfer. Hepatology 1997, 25, 1497-1501.
29. Lau, G.K.; Suri, D.; Liang, R.; Rigopoulou, E.I.; Thomas, M.G.; Mullerova, I.; Nanji, A.; Yuen, S.T.; Williams, R.; Naoumov, N.V. Resolution of chronic hepatitis B and anti-HBs seroconversion in humans by adoptive transfer of immunity to hepatitis B core antigen. Gastroenterology 2002, 122, 614-624.
30. Loggi, E.; Bihl, F.; Chisholm III, J.V.; Biselli, M.; Bontadini, A.; Vitale, G.; Ercolani, G.; Grazi, G.; Pinna, A.D.; Bernardi, M.; Brander, C.; Andreone, P. Anti-HBs re-seroconversion after liver transplantation in a patient with past HBV infection receiving a HBsAg positive graft. J. Hepatol. 2009, 50, 625-630.
31. Thio, C.L.; Thomas, D.L.; Karacki, P.; Gao, X.; Marti, D.; Kaslow, R.A.; Goedert, J.J.; Hilgartner, M.; Strathdee, S.A.; Duggal, P.; O'Brien, S.J.; Astemborski, J.; Carrington, M. Comprehensive analysis of class I and class II HLA antigens and chronic hepatitis B virus infection. J. Virol. 2003, 77, 12083-12087.
32. Thursz, M.; Thomas, H.; Greenwood, B.; Hill, A. Heterozygote advantage for HLA-class II type in hepatitis B virus infection. Nature Genet. 1997, 17, 11-12.
33. Wherry, E.J.; Blattman, J.N.; Murali-Krishna, K.; van der Most, R.; Ahmed, R. Viral persistence alters CD8 T-cell immunodominance and tissue distribution and results in distinct stages of functional impairment. J. Virol. 2003, 77, 4911-4927.
34. Wherry, E.J.; Ha, S.J.; Kaech, S.M.; Haining, W.N.; Sarkar, S.; Kalia, V.; Subramaniam, S.; Blattman, J.N.; Barber, D.L.; Ahmed, R. Molecular Signature of CD8+ T Cell Exhaustion during Chronic Viral Infection. Immunity 2007, 27, 670-684.
35. Lopes, A.R.; Kellam, P.; Das, A.; Dunn, C.; Kwan, A.; Turner, J.; Peppa, D.; Gilson, R.J.; Gehring, A.; Bertoletti, A.; Maini, M. K. Bim-mediated deletion of antigen-specific CD8 T cells in patients unable to control HBV infection. J. Clin. Invest. 2008, 118, 1835-1845.
36. Kakimi, K.; Isogawa, M.; Chung, J.; Sette, A.; Chisari, F.V. Immunogenicity and tolerogenicity of hepatitis B virus structural and nonstructural proteins: implications for immunotherapy of persistent viral infections. J. Virol. 2002, 76, 8609-8620.
37. Maruyama, T.; McLachlan, A.; Iino, S.; Koike, K.; Kurokawa, K.; Milich, D. The serology of chronic hepatitis B infection revisited. J. Clin. Invest. 1993, 91, 2586-2595.
38. Welsh, R. Assessing CD8 T cell number and dysfunction in the presence of antigen. J. Exp. Med. 2001, 193, F19-F22.
39. Ganem, D.; Prince, A.M. Hepatitis B virus infection-natural history and clinical consequences. N. Engl. J. Med. 2004, 350, 1118-1129.
40. Limmer, A.; Ohl, J.; Kurts, C.; Ljunggren, H.-G.; Reiss, Y.; Groettrup, M.; Momburg, F.; Arnold, B.; Knolle, P. Efficient presentation of exogenous antigen by liver endothelial cells to CD8+ T cells results in antigen-specific T cell tolerance. Nature Med. 2000, 6, 1348-1354.
41. Crispe, I.N. Hepatic T cells and liver tolerance. Nat. Rev. Immunol. 2003, 3, 51-62.
42. Bertolino, P.; Bowen, D.; McCaughan, G.; Fazekas de St. Groth, B. Antigen-specific primary activation of CD8+ T cells within the liver. J. Immunol. 2001, 166, 5430-5438.
43. Bertolino, P.; Trescol-Biemont, M.-C.; Rabourdin-Combe, C. Hepatocytes induce functional activation of naive CD8+ T lymphocytes but fail to promote survival. Eur. J. Immunol. 1998, 28, 221-236.
44. Bowen, D.G.; Zen, M.; Holz, L.; Davis, T.; McCaughan, G.W.; Bertolino, P. The site of primary T cell activation is a determinant of the balance between intrahepatic tolerance and immunity. J. Clin. Invest. 2004, 114, 701-712.
45. Murray, D.A.; Crispe, I.N. TNF-alpha controls intrahepatic T cell apoptosis and peripheral T cell numbers. J. Immunol. 2004, 173, 2402-2409.
46. Banchereau, J.; Briere, F.; Caux, C.; Davoust, J.; Lebecque, S.; Liu, Y.J.; Pulendran, B.; Palucka, K. Immunobiology of dendritic cells. Annu. Rev. Immunol. 2000, 18, 767-811.
47. Lew, Y.Y.; Michalak, T.I. In vitro and in vivo infectivity and pathogenicity of the lymphoid cellderived woodchuck hepatitis virus. J. Virol. 2001, 75, 1770-1782.
48. Tavakoli, S.; Schwerin, W.; Rohwer, A.; Hoffmann, S.; Weyer, S.; Weth, R.; Meisel, H.; Diepolder, H.; Geissler, M.; Galle, P.R.; Lohr, H.F.; Bocher, W.O. Phenotype and function of monocyte derived dendritic cells in chronic hepatitis B virus infection. J. Gen. Virol. 2004, 85, 2829-2836.
49. Untergasser, A.; Zedler, U.; Langenkamp, A.; Hosel, M.; Quasdorff, M.; Esser, K.; Dienes, H.P.; Tappertzhofen, B.; Kolanus, W.; Protzer, U. Dendritic cells take up viral antigens but do not support the early steps of hepatitis B virus infection. Hepatology 2006, 43, 539-547.
50. Wang, F.S.; Xing, L.H.; Liu, M.X.; Zhu, C.L.; Liu, H.G.; Wang, H.F.; Lei, Z.Y. Dysfunction of peripheral blood dendritic cells from patients with chronic hepatitis B virus infection. World J. Gastroenterol. 2001, 7, 537-541.
51. Beckebaum, S.; Cicinnati, V.R.; Dworacki, G.; Muller-Berghaus, J.; Stolz, D.; Harnaha, J.; Whiteside, T.L.; Thomson, A.W.; Lu, L.; Fung, J.J.; Bonham, C.A. Reduction in the circulating pDC1/pDC2 ratio and impaired function of ex vivo-generated DC1 in chronic hepatitis B infection. Clin. Immunol. 2002, 104, 138-150.
52. Lohr, H.F.; Pingel, S.; Bocher, W.O.; Bernhard, H.; Herzog-Hauff, S.; Rose-John, S. Reduced virus specific T helper cell induction by autologous dendritic cells in patients with chronic hepatitis B-restoration by exogenous interleukin-12. Clin. Exp. Immunol. 2002, 130, 107-114.
53. van der Molen, R.G.; Sprengers, D.; Binda, R.S.; de Jong, E.C.; Niesters, H.G.; Kusters, J.G.; Kwekkeboom, J.; Janssen, H.L. Functional impairment of myeloid and plasmacytoid dendritic cells of patients with chronic hepatitis B. Hepatology 2004, 40, 738-746.
54. Chen, L.; Zhang, Z.; Chen, W.; Zhang, Z.; Li, Y.; Shi, M.; Zhang, J.; Chen, L.; Wang, S.; Wang, F.S. B7-H1 up-regulation on myeloid dendritic cells significantly suppresses T cell immune function in patients with chronic hepatitis B. J. Immunol. 2007, 178, 6634-6641.
55. Tan, A.T.; Loggi, E.; Boni, C.; Chia, A.; Gehring, A.J.; Sastry, K.S.; Goh, V.; Fisicaro, P.; Andreone, P.; Brander, C.; Lim, S. G.; Ferrari, C.; Bihl, F.; Bertoletti, A. Host ethnicity and virus genotype shape the hepatitis B virus-specific T-cell repertoire. J. Virol. 2008, 82, 10986-10997.
56. Bauer, T.; Gunther, M.; Bienzle, U.; Neuhaus, R.; Jilg, W. Vaccination against hepatitis B in liver transplant recipients: pilot analysis of cellular immune response shows evidence of HBsAgspecific regulatory T cells. Liver Transpl. 2007, 13, 434-442.
57. Manigold, T.; Racanelli, V. T-cell regulation by CD4 regulatory T cells during hepatitis B and C virus infections: facts and controversies. Lancet Infect. Dis. 2007, 7, 804-813.
58. Shevach, E. M. From vanilla to 28 flavors: multiple varieties of T regulatory cells. Immunity 2006, 25, 195-201.
59. van Driel, I.; Ang, D. The role of regulatory T cells in gastrointestinal inflammatory disease. J. Gastroenterol. Hepatol. 2008, 23, 171-177.
60. Yang, G.; Liu, A.; Xie, Q.; Guo, T.B.; Wan, B.; Zhou, B.; Zhang, J.Z. Association of CD4+CD25+Foxp3+ regulatory T cells with chronic activity and viral clearance in patients with hepatitis B. Int. Immunol. 2007, 19, 133-140.
61. Kondo, Y.; Kobayashi, K.; Ueno, Y.; Shiina, M.; Niitsuma, H.; Kanno, N.; Kobayashi, T.; Shimosegawa, T. Mechanism of T cell hyporesponsiveness to HBcAg is associated with regulatory T cells in chronic hepatitis B. World J. Gastroenterol. 2006, 12, 4310-4317.
62. Franzese, O.; Kennedy, P.T.; Gehring, A.J.; Gotto, J.; Williams, R.; Maini, M.K.; Bertoletti, A. Modulation of the CD8+-T-cell response by CD4+ CD25+ regulatory T cells in patients with hepatitis B virus infection. J. Virol. 2005, 79, 3322-3328.
63. Stoop, J.N.; van der Molen, R. G.; Baan, C.C.; van der Laan, L.J.; Kuipers, E.J.; Kusters, J.G.; Janssen, H. L. Regulatory T cells contribute to the impaired immune response in patients with chronic hepatitis B virus infection. Hepatology 2005, 41, 771-778.
64. Xu, D.; Fu, J.; Jin, L.; Zhang, H.; Zhou, C.; Zou, Z.; Zhao, J.M.; Zhang, B.; Shi, M.; Ding, X.; Tang, Z.; Fu, Y.X.; Wang, F.S. Circulating and liver resident CD4+CD25+ regulatory T cells actively influence the antiviral immune response and disease progression in patients with hepatitis B. J. Immunol. 2006, 177, 739-747.
65. Accapezzato, D.; Francavilla, V.; Paroli, M.; Casciaro, M.; Chircu, L.V.; Cividini, A.; Abrignani, S.; Mondelli, M.U.; Barnaba, V. Hepatic expansion of a virus-specific regulatory CD8(+) T cell population in chronic hepatitis C virus infection. J. Clin. Invest. 2004, 113, 963-972.
66. Hyodo, N.; Nakamura, I.; Imawari, M. Hepatitis B core antigen stimulates interleukin-10 secretion by both T cells and monocytes from peripheral blood of patients with chronic hepatitis B virus infection. Clin. Exp. Immunol. 2004, 135, 462-466.
67. Chang, J.J.; Thompson, A.J.; Visvanathan, K.; Kent, S.J.; Cameron, P.U.; Wightman, F.; Desmond, P.; Locarnini, S.A.; Lewin, S.R. The phenotype of hepatitis B virus-specific T cells differ in the liver and blood in chronic hepatitis B virus infection. Hepatology 2007, 46, 1332-1340.
68. Kafrouni, M.I.; Brown, G.R.; Thiele, D.L. Virally infected hepatocytes are resistant to perforindependent CTL effector mechanisms. J. Immunol. 2001, 167, 1566-1574.
69. Guidotti, L.; Chisari, F. Cytokine-induced viral purging-role in viral pathogenesis. Curr. Opin. Microbiol. 1999, 2, 388-391.
70. Isogawa, M.; Furuichi, Y.; Chisari, F.V. Oscillating CD8(+) T cell effector functions after antigen recognition in the liver. Immunity 2005, 23, 53-63.
71. Das, A.; Hoare, M.; Davies, N.; Lopes, A.R.; Dunn, C.; Kennedy, P.T.; Alexander, G.; Finney, H.; Lawson, A.; Plunkett, F.J.; Bertoletti, A.; Akbar, A.N.; Maini, M.K. Functional skewing of the global CD8 T cell population in chronic hepatitis B virus infection. J. Exp. Med. 2008, 205, 2111-2124.
72. Iannacone, M.; Sitia, G.; Ruggeri, Z. M.; Guidotti, L.G. HBV pathogenesis in animal models: recent advances on the role of platelets. J. Hepatol. 2007, 46, 719-726.
73. Lang, P.; Contaldo, C.; Georgiev, P.; El-Badry, A.; Recher, M.; Kurren, M.; Cervantes-Barragan, L.; Ludewig, B.; Calzascia, T.; Bolinger, B.; Merkler, D.; Odermatt, B.; Bader, M.; Graf, R.; Clavien, P.A.; Hegazy, A.; Lohning, M.; Harris, N.; Ohashi, P.S.; Hengartner, H.; Zinkernagel, R.M.; Lang, K.S. Aggravation of viral hepatitis by platelet-derived serotonin. Nat. Med. 2008, 14, 756-761.
74. Maier, H.; Isogawa, M.; Freeman, G.J.; Chisari, F.V. PD-1:PD-L1 interactions contribute to the functional suppression of virus-specific CD8+ T lymphocytes in the liver. J. Immunol. 2007, 178, 2714-2720.
75. Mühlbauer, M.; Fleck, M.; Schütz, C.; Weiss, T.; Froh, M.; Blank, C.; Schölmerich, J.; Hellerbrand, C. PD-L1 is induced in hepatocytes by viral infection and by interferon-α and-γ and mediates T cell apoptosis. J. Hepatol. 2006, 45, 520-528.
76. Gehring, A.J.; Sun, D.; Kennedy, P.T.; Nolte-'t Hoen, E.; Lim, S.G.; Wasser, S.; Selden, C.; Maini, M.K.; Davis, D.M.; Nassal, M.; Bertoletti, A. The level of viral antigen presented by hepatocytes influences CD8 T-cell function. J. Virol. 2007, 81, 2940-2949.
77. Kim, J.V.; Kang, S.S.; Dustin, M.L.; McGavern, D.B. Myelomonocytic cell recruitment causes fatal CNS vascular injury during acute viral meningitis. Nature 2009, 475, 191-195.
78. Sitia, G.; Isogawa, M.; Kakimi, K.; Wieland, S.F.; Chisari, F.V.; Guidotti, L.G. Depletion of neutrophils blocks the recruitment of antigen-nonspecific cells into the liver without affecting the antiviral activity of hepatitis B virus-specific cytotoxic T lymphocytes. Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 13717-13722.
79. Sitia, G.; Isogawa, M.; Iannacone, M.; Campbell, I.L.; Chisari, F.V.; Guidotti, L.G. MMPs are required for recruitment of antigen-non specific mononuclear cells into the liver by CTLs. J. Clin. Invest. 2004, 113, 1158-1167.
80. Iannacone, M.; Sitia, G.; Isogawa, M.; Marchese, P.; Castro, M.G.; Lowenstein, P.R.; Chisari, F.V.; Ruggeri, Z.M.; Guidotti, L.G. Platelets mediate cytotoxic T lymphocyte-induced liver damage. Nat. Med. 2005, 11, 1167-1169.