Hepatic NK, NKT, and T cells

Liver Immunology: Principles and Practice

Volumn , Issue , 2007, Pages 71-82

  Ahlenstiel, Golo ^a,b   Rehermann, Barbara ^a,b  

^a NIDDK   (United States)

^b NATIONAL INSTITUTES OF HEALTH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 84886243574     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1007/978-1-59745-518-3_7     Document Type: Chapter

References (126)

1. Cantor HM, Dumont AE. Hepatic suppression of sensitization to antigen absorbed into the portal system. Nature 1967; 215:744-745
2. Wang C, Sun J, Wang L, Li L, Horvat M, Sheil R. Combined liver and pancreas transplantation induces pancreas allograft tolerance. Transplant Proc 1997; 29:1145-1146
3. Bertolino P, Bowen DG, McCaughan GW, Fazekas De St Groth B. Antigen-specific primary activation of CD8(+) T cells within the liver. J Immunol 2001; 166:5430-5438
4. Liu ZX, Govindarajan S, Okamoto S, Dennert G. Fas-mediated apoptosis causes elimination of virus-specific cytotoxic T cells in the virus-infected liver. J Immunol 2001; 166:3035-3041
5. Sheth K, Bankey P. The liver as an immune organ. Curr Opin Crit Care 2001; 7:99-104
6. Wick MJ, Leithauser F, Reimann J. The hepatic immune system. Crit Rev Immunol 2002; 22:47-103
7. Wisse E. An electron microscopic study of the fenestrated endothelial lining of rat liver sinusoids. J Ultrastruct Res 1970; 31:125-150
8. Emoto M, Miyamoto M, Namba K, et al. Participation of leukocyte function-associated antigen-1 and NK cells in the homing of thymic CD8+NKT cells to the liver. Eur J Immunol 2000; 30: 3049-3056
9. Hata K, Zhang XR, Iwatsuki S, Van Thiel DH, Herberman RB, Whiteside TL. Isolation, phenotyping, and functional analysis of lymphocytes from human liver. Clin Immunol Immunopathol 1990; 56:401-419
10. Doherty DG, O'Farrelly C. Innate and adaptive lymphoid cells in the human liver. Immunol Rev 2000; 174:5-20
11. 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
12. Bendelac A, Lantz O, Quimby ME, Yewdell JW, Bennink JR, Brutkiewicz RR. CD1 recognition by mouse NK1+ T lymphocytes. Science 1995; 268:863-865
13. Emoto M, Kaufmann SH. Liver NKT cells: An account of heterogeneity. Trends Immunol 2003; 24:364-369
14. Exley M, Koziel M. To be or not to be NKT: Natural killer T cells in the liver. Hepatology 2004; 40:1033-1040
15. O'Farrelly C, Crispe IN. Prometheus through the looking glass: Reflections on the hepatic immune system. Immunol Today 1999; 20:394-398
16. Huang L, Sye K, Crispe IN. Proliferation and apoptosis of B220+CD4-CD8-TCR alpha beta intermediate T cells in the liver of normal adult mice: Implication for lpr pathogenesis. Int Immunol 1994; 6:533-540
17. Huang L, Soldevila G, Leeker M, Flavell R, Crispe IN. The liver eliminates T cells undergoing antigen-triggered apoptosis in vivo. Immunity 1994; 1:741-749
18. Masuda T, Ohteki T, Abo T, et al. Expansion of the population of double negative CD4-8- T alpha beta-cells in the liver is a common feature of autoimmune mice. J Immunol 1991; 147:2907-2912
19. Bandeira A, Itohara S, Bonneville M, et al. Extrathymic origin of intestinal intraepithelial lymphocytes bearing T-cell antigen receptor gamma delta. Proc Natl Acad Sci USA 1991; 88:43-47
20. Moretta L, Ciccone E, Mingari MC, Biassoni R, Moretta A. Human natural killer cells: Origin, clonality, specificity, receptors. Adv Immunol 1994; 55:341-358
21. Salazar-Mather TP, Orange JS, Biron CA. Early murine cytomegalovirus (MCMV) infection induces liver natural killer (NK) cell inflammation and protection through macrophage inflammatory protein 1alpha (MIP-1alpha)-dependent pathways. J Exp Med 1998; 187:1-14
22. Biron CA, Brossay L. NK cells and NKT cells in innate defense against viral infections. Curr Opin Immunol 2001; 13:458-464
23. Wu J, Lanier LL. Natural killer cells and cancer. Adv Cancer Res 2003; 90:127-156
24. Trinchieri G. Biology of natural killer cells. Adv Immunol 1989; 47:187-376
25. Cooper MA, Fehniger TA, Fuchs A, Colonna M, Caligiuri MA. NK cell and DC interactions. Trends Immunol 2004; 25:47-52
26. Itoh Y, Morita A, Nishioji K, et al. Time course profile and celltype- specific production of monokine induced by interferon-gamma in Concanavalin A-induced hepatic injury in mice: Comparative study with interferon-inducible protein-10. Scand J Gastroenterol 2001; 36:1344-1351
27. Zingoni A, Sornasse T, Cocks BG, Tanaka Y, Santoni A, Lanier LL. NK cell regulation of T cell-mediated responses. Mol Immunol 2005; 42:451-454
28. Campbell JJ, Qin S, Unutmaz D, et al. Unique subpopulations of CD56+ NK and NK-T peripheral blood lymphocytes identified by chemokine receptor expression repertoire. J Immunol 2001; 166: 6477-6482
29. He XS, Draghi M, Mahmood K, et al. T cell-dependent production of IFN-gamma by NK cells in response to influenza A virus. J Clin Invest 2004; 114:1812-1819
30. Cooper MA, Fehniger TA, Caligiuri MA. The biology of human natural killer-cell subsets. Trends Immunol 2001; 22:633-640
31. Jacobs R, Hintzen G, Kemper A, et al. CD56bright cells differ in their KIR repertoire and cytotoxic features from CD56dim NK cells. Eur J Immunol 2001; 31:3121-3127
32. Fehniger TA, Cooper MA, Nuovo GJ, et al. CD56bright natural killer cells are present in human lymph nodes and are activated by T cellderived IL-2: A potential new link between adaptive and innate immunity. Blood 2003; 101:3052-3057
33. Hu PF, Hultin LE, Hultin P, et al. Natural killer cell immunodeficiency in HIV disease is manifest by profoundly decreased numbers of CD16+CD56+ cells and expansion of a population of CD16dimCD56- cells with low lytic activity. J Acquir Immune Defic Syndr Hum Retrovirol 1995; 10:331-340
34. Mavilio D, Benjamin J, Daucher M, et al. Natural killer cells in HIV-1 infection: Dichotomous effects of viremia on inhibitory and activating receptors and their functional correlates. Proc Natl Acad Sci USA 2003; 100:15,011-15,016
35. Ljunggren HG, Karre K. In search of the 'missing self': MHC molecules and NK cell recognition. Immunol Today 1990; 11: 237-244
36. Tomasello E, Blery M, Vely F, Vivier E. Signaling pathways engaged by NK cell receptors: Double concerto for activating receptors, inhibitory receptors and NK cells. Semin Immunol 2000; 12: 139-147
37. Biassoni R, Pessino A, Malaspina A, et al. Role of amino acid position 70 in the binding affinity of p50.1 and p58.1 receptors for HLA-Cw4 molecules. Eur J Immunol 1997; 27:3095-3099
38. Cantoni C, Bottino C, Vitale M, et al. NKp44, a triggering receptor involved in tumor cell lysis by activated human natural killer cells, is a novel member of the immunoglobulin superfamily. J Exp Med 1999; 189:787-796
39. Biron CA, Nguyen KB, Pien GC, Cousens LP, Salazar-Mather TP. Natural killer cells in antiviral defense: Function and regulation by innate cytokines. Annu Rev Immunol 1999; 17:189-220
40. Orange JS, Wang B, Terhorst C, Biron CA. Requirement for natural killer cell-produced interferon gamma in defense against murine cytomegalovirus infection and enhancement of this defense pathway by interleukin 12 administration. J Exp Med 1995; 182: 1045-1056
41. Habu S, Akamatsu K, Tamaoki N, Okumura K. In vivo significance of NK cell on resistance against virus (HSV-1) infections in mice. J Immunol 1984; 133:2743-2747
42. Stein-Streilein J, Guffee J. In vivo treatment of mice and hamsters with antibodies to asialo GM1 increases morbidity and mortality to pulmonary influenza infection. J Immunol 1986; 136:1435-1441
43. Godeny EK, Gauntt CJ. Involvement of natural killer cells in coxsackievirus B3-induced murine myocarditis. J Immunol 1986; 137: 1695-1702
44. McRae BL, Semnani RT, Hayes MP, van Seventer GA. Type I IFNs inhibit human dendritic cell IL-12 production and Th1 cell development. J Immunol 1998; 160:4298-4304
45. Cousens LP, Orange JS, Su HC, Biron CA. Interferon-alpha/beta inhibition of interleukin 12 and interferon-gamma production in vitro and endogenously during viral infection. Proc Natl Acad Sci USA 1997; 94:634-639
46. Nguyen KB, Cousens LP, Doughty LA, Pien GC, Durbin JE, Biron CA. Interferon alpha/beta-mediated inhibition and promotion of interferon gamma: STAT1 resolves a paradox. Nat Immunol 2000; 1:70-76
47. Tay CH, Welsh RM. Distinct organ-dependent mechanisms for the control of murine cytomegalovirus infection by natural killer cells. J Virol 1997; 71:267-275
48. Salazar-Mather TP, Hamilton TA, Biron CA. A chemokine-tocytokine- To-chemokine cascade critical in antiviral defense. J Clin Invest 2000; 105:985-993
49. Salazar-Mather TP, Lewis CA, Biron CA. Type I interferons regulate inflammatory cell trafficking and macrophage inflammatory protein 1alpha delivery to the liver. J Clin Invest 2002; 110:321-330
50. Tomasec P, Braud VM, Rickards C, et al. Surface expression of HLA-E, an inhibitor of natural killer cells, enhanced by human cytomegalovirus gpUL40. Science 2000; 287:1031
51. Cosman D, Mullberg J, Sutherland CL, et al. ULBPs, novel MHC class I-related molecules, bind to CMV glycoprotein UL16 and stimulate NK cytotoxicity through the NKG2D receptor. Immunity 2001; 14:123-133
52. Carnaud C, Lee D, Donnars O, et al. Cutting edge: Cross-talk between cells of the innate immune system: NKT cells rapidly activate NK cells. J Immunol 1999; 163:4647-4650
53. Porcelli SA, Modlin RL. The CD1 system: Antigen-presenting molecules for T cell recognition of lipids and glycolipids. Annu Rev Immunol 1999; 17:297-329
54. Castano AR, Tangri S, Miller JE, et al. Peptide binding and presentation by mouse CD1. Science 1995; 269:223-226
55. Kawano T, Cui J, Koezuka Y, et al. CD1d-restricted and TCRmediated activation of valpha14 NKT cells by glycosylceramides. Science 1997; 278:1626-1629
56. Brossay L, Chioda M, Burdin N, et al. CD1d-mediated recognition of an alpha-galactosylceramide by natural killer T cells is highly conserved through mammalian evolution. J Exp Med 1998; 188: 1521-1528
57. Brigl M, Bry L, Kent SC, Gumperz JE, Brenner MB. Mechanism of CD1d-restricted natural killer T cell activation during microbial infection. Nat Immunol 2003; 4:1230-1237
58. Exley M, Porcelli S, Furman M, Garcia J, Balk S. CD161 (NKRP1A) costimulation of CD1d-dependent activation of human T cells expressing invariant V alpha 24 J alpha Q T cell receptor alpha chains. J Exp Med 1998; 188:867-876
59. Godfrey DI, Kronenberg M. Going both ways: Immune regulation via CD1d-dependent NKT cells. J Clin Invest 2004; 114:1379-1388
60. Bendelac A, Rivera MN, Park SH, Roark JH. Mouse CD1-specific NK1 T cells: Development, specificity, and function. Annu Rev Immunol 1997; 15:535-562
61. Kumagai K, Takeda K, Hashimoto W, et al. Interleukin-12 as an inducer of cytotoxic effectors in anti-tumor immunity. Int Rev Immunol 1997; 14:229-256
62. Cui J, Shin T, Kawano T, et al. Requirement for Valpha14 NKT cells in IL-12-mediated rejection of tumors. Science 1997; 278: 1623-1626
63. Kawamura T, Takeda K, Mendiratta SK, et al. Critical role of NK1+T cells in IL-12-induced immune responses in vivo. J Immunol 1998; 160:16-19
64. Metelitsa LS, Naidenko OV, Kant A, et al. Human NKT cells mediate antitumor cytotoxicity directly by recognizing target cell CD1d with bound ligand or indirectly by producing IL-2 to activate NK cells. J Immunol 2001; 167:3114-3122
65. Kitamura H, Iwakabe K, Yahata T, et al. The natural killer T (NKT) cell ligand alpha-galactosylceramide demonstrates its immunopotentiating effect by inducing interleukin (IL)-12 production by dendritic cells and IL-12 receptor expression on NKT cells. J Exp Med 1999; 189:1121-1128
66. Fujii S, Shimizu K, Smith C, Bonifaz L, Steinman RM. Activation of natural killer T cells by alpha-galactosylceramide rapidly induces the full maturation of dendritic cells in vivo and thereby acts as an adjuvant for combined CD4 and CD8 T cell immunity to a coadministered protein. J Exp Med 2003; 198: 267-279
67. Kenna T, Golden-Mason L, Porcelli SA, et al. NKT cells from normal and tumor-bearing human livers are phenotypically and functionally distinct from murine NKT cells. J Immunol 2003; 171:1775-1779
68. Kronenberg M, Gapin L. The unconventional lifestyle of NKT cells. Nat Rev Immunol 2002; 2:557-568
69. Smyth MJ, Crowe NY, Hayakawa Y, Takeda K, Yagita H, Godfrey DI. NKT cells - conductors of tumor immunity? Curr Opin Immunol 2002; 14:165-171
70. Karadimitris A, Gadola S, Altamirano M, et al. Human CD1dglycolipid tetramers generated by in vitro oxidative refolding chromatography. Proc Natl Acad Sci USA 2001; 98:3294-3298
71. Grubor-Bauk B, Simmons A, Mayrhofer G, Speck PG. Impaired clearance of herpes simplex virus type 1 from mice lacking CD1d or NKT cells expressing the semivariant V alpha 14-J alpha 281 TCR. J Immunol 2003; 170:1430-1434
72. Behar SM, Dascher CC, Grusby MJ, Wang CR, Brenner MB. Susceptibility of mice deficient in CD1D or TAP1 to infection with Mycobacterium tuberculosis. J Exp Med 1999; 189:1973-1980
73. Kumar H, Belperron A, Barthold SW, Bockenstedt LK. Cutting edge: CD1d deficiency impairs murine host defense against the spirochete, Borrelia burgdorferi. J Immunol 2000; 165: 4797-4801
74. Eberl G, MacDonald HR. Rapid death and regeneration of NKT cells in anti-CD3epsilon- or IL-12-treated mice: A major role for bone marrow in NKT cell homeostasis. Immunity 1998; 9: 345-353
75. Kakimi K, Guidotti LG, Koezuka Y, Chisari FV. Natural killer T cell activation inhibits hepatitis B virus replication In vivo. J Exp Med 2000; 192:921-930
76. Exley MA, Bigley NJ, Cheng O, et al. CD1d-reactive T-cell activation leads to amelioration of disease caused by diabetogenic encephalomyocarditis virus. J Leukoc Biol 2001; 69:713-718
77. Baron JL, Gardiner L, Nishimura S, Shinkai K, Locksley R, Ganem D. Activation of a nonclassical NKT cell subset in a transgenic mouse model of hepatitis B virus infection. Immunity 2002; 16:583-594
78. Osman Y, Kawamura T, Naito T, et al. Activation of hepatic NKT cells and subsequent liver injury following administration of alphagalactosylceramide. Eur J Immunol 2000; 30:1919-1928
79. Toyabe S, Seki S, Iiai T, et al. Requirement of IL-4 and liver NK1+ T cells for concanavalin A-induced hepatic injury in mice. J Immunol 1997; 159:1537-1542
80. Gonzalo JA, Delaney T, Corcoran J, Goodearl A, Gutierrez-Ramos JC, Coyle AJ. Cutting edge: The related molecules CD28 and inducible costimulator deliver both unique and complementary signals required for optimal T cell activation. J Immunol 2001; 166:1-5
81. Bertolino P, McCaughan G, Bowen DG. Role of primary intrahepatic T cell activation in the liver tolerance effect. Immunol Cell Biol 2002; 80:84-92
82. Bertolino P, Trescol-Biemont MC, Rabourdin-Combe C. Hepatocytes induce functional activation of naive CD8+ T lymphocytes but fail to promote survival. Eur J Immunol 1998; 28:221-236
83. Bowen DG, Zen M, Holz L, Davis T, McCaughan GW, 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
84. Hiramatsu N, Hayashi N, Katayama K, et al. Immunohistochemical detection of Fas antigen in liver tissue of patients with chronic hepatiits C. Hepatology 1994; 19:1354-1359
85. Mita E, Hayashi N, Iio S, et al. Role of Fas ligand in apoptosis induced by hepatitis C virus infection. Biochem Biophys Res Commun 1994; 204:468-474
86. Lohman BL, Razvi ES, Welsh RM. T-lymphocyte downregulation after acute viral infection is not dependent on CD95 (Fas) receptorligand interactions. J Virol 1996; 70:8199-8203
87. 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 1990; 171:941-946
88. Cuturi MC, Murphy M, Costa-Giomi MP, Weinmann R, Perussia B, Trinchieri G. Independent regulation of tumor necrosis factor and lymphotoxin production by human peripheral blood lymphocytes. J Exp Med 1987; 165:1581-1594
89. Sung S-S, Bjordahl JM, Wang CY, Kao HT, Fu SM. Production of tumor necrosis factor/cachectin by human T cell lines and peripheral blood T lymphocytes stimulated by phorbolmyristate acetate and anti-CD3 antibody. J Exp Med 1988; 168:1539-1551
90. Steffen M, Ottmann O, Moore M. Simultaneous production of tumor necrosis factor-alpha and lymphotoxin by normal T cells after induction with IL-2 and anti-T3. J Immunol 1988; 140: 2621-2640
91. Vassalli P. The pathophysiology of tumor necrosis factors. Annu Rev Immunol 1992; 10:411-452
92. Koziel MJ, 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 1995; 96:2311-2321
93. 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 1997; 158: 5283-5291
94. Jenne DE, Tschopp J. Granzymes: A family of serine proteases in granules of cytolytic T lymphocytes. Curr Top Microbiol Immunol 1989; 140:33-47
95. Tschopp J, Nabholz M. Perforin-mediated target cell lysis by cytolytic T lymphocytes. Annu Rev Immunol 1990; 8:279-302
96. Darmon AJ, Ley TJ, Nicholson DW, Bleackley RC. Cleavage of CPP32 by granzyme B represents a critical role for granzyme B in the induction of target cell DNA fragmentation. J Biol Chem 1996; 271:21,709-21,712
97. Song Q, Burrows S, Smith G, et al. Interleukin-1 beta-converting enzyme-like protease cleaves DNA-dependent protein kinase in cytotoxic T cell killing. J Exp Med 1996; 184:619-626
98. Duke RC, Chervenak R, Cohen JJ. Endogenous endonucleaseinduced DNA fragmentation: An early event in cell-mediated cytolysis. Proc Natl Acad Sci USA 1983; 80:6361-6365
99. Bertoletti A, D'Elios MM, Boni C, et al. Different cytokine profiles of intrahepatic T cells in chronic hepatitis B and hepatitis C virus infections. Gastroenterology 1997; 112:193-199
100. Guidotti LG, Chisari FV. To kill or to cure: Options in host defense against viral infection. Curr Opin Immunol 1996; 8:478-483
101. Guidotti LG, Ando K, Hobbs MV, et al. Cytotoxic T lymphocytes inhibit hepatitis B virus gene expression by a noncytolytic mechanism in transgenic mice. Proc Natl Acad Sci USA 1994; 91: 3764-3768
102. Guidotti LG, Ishikawa T, Hobbs MV, Matzke B, Schreiber R, Chisari FV. Intracellular inactivation of the hepatitis B virus by cytotoxic T lymphocytes. Immunity 1996; 4:35-36
103. Guidotti LG, Rochford R, Chung J, Shapiro M, Purcell R, Chisari FV. Viral clearance without destruction of infected cells during acute HBV infection. Science 1999; 284:825-829
104. Spriggs MK, Koller BH, Sato T, et al. Beta 2-microglobulin-, CD8+ T-cell-deficient mice survive inoculation with high doses of vaccinia virus and exhibit altered IgG responses. Proc Natl Acad Sci USA 1992; 89:6070-6074
105. Ramsay AJ, Ruby J, Ramshaw IA. A case for cytokines as effector molecules in the resolution of virus infection. Immunol Today 1993; 14:155-157
106. Kagi D, Ledermann B, Burki K, et al. Cytotoxicity mediated by T cells and natural killer cells is greatly impaired in perforin-deficient mice. Nature 1994; 369:31-37
107. Marra F, DeFranco R, Grappone C, et al. Increased expression of monocyte chemotactic protein-1 during active hepatic fibrogenesis: Correlation with monocyte infiltration. Am J Pathol 1998; 152: 423-430
108. Nakamoto Y, Guidotti LG, Kuhlen CV, Fowler P, Chisari FV. Immune pathogenesis of hepatocellular carcinoma. J Exp Med 1998; 188:341-350
109. Larkin J, Clayton M, Sun B, et al. Hepatitis B virus transgenic mouse model of chronic liver disease. Nat Med 1999; 5:907-912
110. Ando K, Moriyama T, Guidotti LG, et al. Mechanisms of class I restricted immunopathology. A transgenic mouse model of fulminant hepatitis. J Exp Med 1993; 178:1541-1554
111. Kakimi K, Lane TE, Wieland S, et al. Blocking chemokine responsive to gamma-2/interferon (IFN)-gamma inducible protein and monokine induced by IFN-gamma activity in vivo reduces the pathogenetic but not the antiviral potential of hepatitis B virus-specific cytotoxic T lymphocytes. J Exp Med 2001; 194: 1755-1766
112. Shields PL, Morland C, Salmon M, Qin S, Hubscher S, Adams DH. Chemokine and chemokine receptor interactions provide a mechanism for selective T cell recruitment to specific liver compartments within HCV-Infected Liver. J Immunol 1999; 163: 6236-6243
113. Kaneko Y, Harada M, Kawano T, et al. Augmentation of Valpha14 NKT cell-mediated cytotoxicity by interleukin 4 in an autocrine mechanism resulting in the development of concanavalin A-induced hepatitis. J Exp Med 2000; 191:105-114
114. Mehal WZ, Juedes AE, Crispe IN. Selective retention of activated CD8+ T cells by the normal liver. J Immunol 1999; 163: 3202-3210
115. Sitia G, Isogawa M, Kakimi K, Wieland SF, Chisari FV, Guidotti LG. 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 USA 2002; 99:13,717-13,722
116. Sitia G, Isogawa M, Iannacone M, Campbell IL, Chisari FV, Guidotti LG. MMPs are required for recruitment of antigen-nonspecific mononuclear cells into the liver by CTLs. J Clin Invest 2004; 113:1158-1167
117. Bianchi L. Liver biopsy interpretation in hepatitis. Part II: Histopathology and classification of acute and chronic viral hepatitis/ differential diagnosis. Pathol Res Pract 1983; 178:180-213
118. Rehermann B, Nascimbeni M. Immunology of hepatitis B virus and hepatitis C virus infection. Nat Rev Immunol 2005; 5:215-229
119. Ferrari C, Penna A, Giuberti T, et al. Intrahepatic, nucleocapsid antigen-specific T cells in chronic active hepatitis B. J Immunol 1987; 139:2050-2058
120. Barnaba V, Franco A, Alberti AB 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
121. Moriyama T, Guilhot S, Klopchin K, et al. Immunobiology and pathogenesis of hepatocellular injury in hepatitis B virus transgenic mice. Science 1990; 248:361-364
122. Kita H, Mackay IR, Van De Water J, Gershwin ME. The lymphoid liver: Considerations on pathways to autoimmune injury. Gastroenterology 2001; 120:1485-1501
123. Galperin C, Gershwin ME. Immunopathology of primary biliary cirrhosis. Baillieres Clin Gastroenterol 1996; 10:461-481
124. Lohr HF, Schlaak JF, Lohse AW, et al. Autoreactive CD4+ LKMspecific and anticlonotypic T-cell responses in LKM-1 antibodypositive autoimmune hepatitis. Hepatology 1996; 24:1416-1421
125. Liu ZX, Govindarajan S, Okamoto S, Dennert G. Fas-mediated apoptosis causes elimination of virus-specific cytotoxic T cells in the virus-infected liver. J Immunol 2001; 166:3035-3041
126. Racanelli V, Rehermann B. The liver as an immunological organ. Hepatology. 2006; 43(2 Suppl 1):S54-S62