T cells with regulatory activity in hepatitis C virus infection: What we know and what we don't

Journal of Leukocyte Biology

Volumn 84, Issue 3, 2008, Pages 614-622

  Dolganiuc, Angela ^a   Szabo, Gyongyi ^a  

^a UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL   (United States)

Author keywords

CD8+; FoxP3; IL 10; Liver; TGF ; Th3; Tr1; Tregs

Indexed keywords

INTERLEUKIN 10; TOLL LIKE RECEPTOR;

ANTIGEN SPECIFICITY; CD4+ CD25+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELL ACTIVATION; CELL HETEROGENEITY; CELL INTERACTION; CELL POPULATION; HEPATITIS C; HEPATITIS C VIRUS; HUMAN; IMMUNE RESPONSE; PATHOGENESIS; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; REVIEW; TH3 CELL; VIRUS INFECTION;

ANIMALS; HEPACIVIRUS; HEPATITIS C; HUMANS; IMMUNITY, CELLULAR; T-LYMPHOCYTES, REGULATORY; VIRAL CORE PROTEINS;

HEPATITIS C VIRUS;

EID: 50849115190     PISSN: 07415400     EISSN: None     Source Type: Journal    
DOI: 10.1189/jlb.1107770     Document Type: Review

References (93)

1. NIH Consensus Statement on Management of Hepatitis C: 2002. (2002) NIH Consens State Sci. Statements 19, 1-46.
2. Spengler, U., Nattermann, J. (2007) Immunopathogenesis in hepatitis C virus cirrhosis. Clin. Sci. (Lond.) 112, 141-155.
3. Chang, K. M. (2007) Regulatory T cells in hepatitis C virus infection. Hepatol. Res. 37 (Suppl. 3), S327-S330.
4. Racanelli, V., Rehermann, B. (2003) Hepatitis C virus infection: when silence is deception. Trends Immunol. 24, 456-464.
5. Chang, K M. (2003) Immunopathogenesis of hepatitis C virus infection. Clin. Liver Dis. 7, 89-105.
6. Bowen, D. G., Walker, C. M. (2005) Adaptive immune responses in acute and chronic hepatitis C virus infection. Nature 436, 946-952.
7. Auffermann-Gretzinger, S., Keeffe, E. B., Levy, S. (2001) Impaired dendritic cell maturation in patients with chronic, but not resolved, hepatitis C virus infection. Blood 97, 3171-3176.
8. Dolganiuc, A., Kodys, K., Kopasz, A., Marshall, C., Do, T., Romics Jr., L., Mandrekar, P., Zapp, M., Szabo, G. (2003) Hepatitis C virus core and nonstructural protein 3 proteins induce pro- and anti-inflammatory cytokines and inhibit dendritic cell differentiation. J. Immunol. 170, 5615-5624.
9. Bain, C., Fatmi, A., Zoulim, F., Zarski, J. P., Trépo, C., Inchauspé, G. (2001) Impaired allostimulatory function of dendritic cells in chronic hepatitis C infection. Gastroenterology 120, 512-524.
10. Kanto, T., Hayashi, N., Takehara, T., Tatsumi, T., Kuzushita, N., Ito, A., Sasaki, Y., Kasahara, A., Hori, M. (1999) Impaired allostimulatory capacity of peripheral blood dendritic cells recovered from hepatitis C virus-infected individuals. J. Immunol. 162, 5584-5591.
11. Gelderblom, H. C., Nijhuis, L. E., de Jong, E. C., te Velde, A. A., Pajkrt, D., Reesink, H. W., Beld, M. G., van Deventer, S. J., Jansen, P. L. (2007) Monocyte-derived dendritic cells from chronic HCV patients are not infected but show an immature phenotype and aberrant cytokine profile. Liver Int. 27, 944-953.
12. Dolganiuc, A., Chang, S., Kodys, K., Mandrekar, P., Bakis, G., Cormier, M., Szabo, G. (2006) Hepatitis C virus (HCV) core protein-induced, monocyte-mediated mechanisms of reduced IFN-α and plasmacytoid dendritic cell loss in chronic HCV infection. J. Immunol. 177, 6758-6768.
13. Della Bella, S., Crosignani, A., Riva, A., Presicce, P., Benetti, A., Longhi, R., Podda, M., Villa, M. L. (2007) Decrease and dysfunction of dendritic cells correlate with impaired hepatitis C virus-specific CD4+ T-cell proliferation in patients with hepatitis C virus infection. Immunology 121, 283-292.
14. Larsson, M., Babcock, E., Grakoui, A., Shoukry, N., Lauer, G., Rice, C., Walker, C., Bhardwaj, N. (2004) Lack of phenotypic and functional impairment in dendritic cells from chimpanzees chronically infected with hepatitis C virus. J. Virol. 78, 6151-6161.
15. Longman, R. S., Talal, A. H., Jacobson, I. M., Albert, M. L., Rice, C. M. (2004) Presence of functional dendritic cells in patients chronically infected with hepatitis C virus. Blood 103, 1026-1029.
16. Woodland, D. L., Dutton, R. W. (2003) Heterogeneity of CD4(+) and CD8(+) T cells. Curr. Opin. Immunol. 15, 336-342.
17. Salgame, P., Abrams, J. S., Clayberger, C. (1991) Differing lymphokine profiles of functional subsets of human CD4 and CD8 T cell clones. Science 254, 279-282.
18. Fehérvári, Z., Sakaguchi, S. (2004) Control of Foxp3+ CD25+CD4+ regulatory cell activation and function by dendritic cells. Int. Immunol. 16, 1769-1780.
19. Barrat, F. J., Cua, D. J., Boonstra, A., Richards, D. F., Crain, C., Savelkoul, H. F., de Waal-Malefyt, R., Coffman, R. L., Hawrylowicz, C. M., O'Garra, A. (2002) In vitro generation of interleukin 10-producing regulatory CD4(+) T cells is induced by immunosuppressive drugs and inhibited by T helper type 1 (Th1)- and Th2-inducing cytokines. J. Exp. Med. 195, 603-616.
20. Cerwenka, A., Swain, S. L. (1999) TGF-β1: immunosuppressant and viability factor for T lymphocytes. Microbes Infect. 1, 1291-1296.
21. Vukmanovic-Stejic, M., Zhang, Y., Cook, J. E., Fletcher, J. M., McQuaid, A., Masters, J. E., Rustin, M. H., Taams, L. S., Beverley, P. C., Macallan, D. C., Akbar, A. N. (2006) Human CD4+ CD25hi Foxp3+ regulatory T cells are derived by rapid turnover of memory populations in vivo. J. Clin. Invest. 116, 2423-2433.
22. Horwitz, D. A., Zheng, S. G., Gray, J. D. (2003) The role of the combination of IL-2 and TGF-β or IL-10 in the generation and function of CD4+ CD25+ and CD8+ regulatory T cell subsets. J. Leukoc. Biol. 74, 471-478.
23. Lehmann, J., Huehn, J., de la Rosa, M., Maszyna, F., Kretschmer, U., Krenn, V., Brunner, M., Scheffold, A., Hamann, A. (2002) Expression of the integrin α Eβ 7 identifies unique subsets of CD25+ as well as CD25-regulatory T cells. Proc. Natl. Acad. Sci. USA 99, 13031-13036.
24. Graca, L., Thompson, S., Lin, C. Y., Adams, E., Cobbold, S. P., Waldmann, H. (2002) Both CD4(+)CD25(+) and CD4(+)CD25(-) regulatory cells mediate dominant transplantation tolerance. J. Immunol. 168, 5558-5565.
25. Rouse, B. T., Sarangi, P. P., Suvas, S. (2006) Regulatory T cells in virus infections. Immunol. Rev. 212, 272-286.
26. Boettler, T., Spangenberg, H. C., Neumann-Haefelin, C., Panther, E., Urbani, S., Ferrari, C., Blum, H. E., von Weizsäcker, F., Thimme, R. (2005) T cells with a CD4+CD25+ regulatory phenotype suppress in vitro proliferation of virus-specific CD8+ T cells during chronic hepatitis C virus infection. J. Virol. 79, 7860-7867.
27. Sugimoto, K., Ikeda, F., Stadanlick, J., Nunes, F. A., Alter, H. J., Chang, K. M. (2003) Suppression of HCV-specific T cells without differential hierarchy demonstrated ex vivo in persistent HCV infection. Hepatology 38, 1437-1448.
28. Rushbrook, S. M., Ward, S. M., Unitt, E., Vowler, S. L., Lucas, M., Klenerman, P., Alexander, G. J. (2005) Regulatory T cells suppress in vitro proliferation of virus-specific CD8+ T cells during persistent hepatitis C virus infection. J. Virol. 79, 7852-7859.
29. Bolacchi, F., Sinistro, A., Ciaprini, C., Demin, F., Capozzi, M., Carducci, F. C., Drapeau, C. M., Rocchi, G., Bergamini, A. (2006) Increased hepatitis C virus (HCV)-specific CD4+CD25+ regulatory T lymphocytes and reduced HCV-specific CD4+ T cell response in HCV-infected patients with normal versus abnormal alanine aminotransferase levels. Clin. Exp. Immunol. 144, 188-196.
30. Li, S., Jones, K. L., Woollard, D. J., Dromey, J., Paukovics, G., Plebanski, M., Gowans, E. J. (2007) Defining target antigens for CD25+ FOXP3 + IFN-γ-regulatory T cells in chronic hepatitis C virus infection. Immunol. Cell Biol. 85, 197-204.
31. Cabrera, R., Tu, Z., Xu, Y., Firpi, R. J., Rosen, H. R., Liu, C., Nelson, D. R. (2004) An immunomodulatory role for CD4(+)CD25(+) regulatory T lymphocytes in hepatitis C virus infection. Hepatology 40, 1062-1071.
32. Yang, J. H., Zhang, Y. X., Yu, R. B., Su, C., Sun, N. X. (2006) CD4+ CD25+ regulatory T cells suppress CD4+ T cell responses in patients with persistent hepatitis C virus infection. Zhonghua Nei Ke Za Zhi 45, 29-33.
33. Manigold, T., Shin, E. C., Mizukoshi, E., Mihalik, K., Murthy, K. K., Rice, C. M., Piccirillo, C. A., Rehermann, B. (2006) Foxp3+CD4+CD25+ T cells control virus-specific memory T cells in chimpanzees that recovered from hepatitis C. Blood 107, 4424-4432.
34. Perrella, A., Vitiello, L., Atripaldi, L., Conti, P., Sbreglia, C., Altamura, S., Patarino, T., Vela, R., Morelli, G., Bellopede, P., Alone, C., Racioppi, L., Perrella, O. (2006) Elevated CD4+/CD25+ T cell frequency and function during acute hepatitis C presage chronic evolution. Gut 55, 1370-1371.
35. Ulsenheimer, A., Gerlach, J. T., Gruener, N. H., Jung, M. C., Schirren, C. A., Schraut, W., Zachoval, R., Pape, G. R., Diepolder, H. M. (2003) Detection of functionally altered hepatitis C virus-specific CD4 T cells in acute and chronic hepatitis C. Hepatology 37, 1189-1198.
36. Boyer, O., Saadoun, D., Abriol, J., Dodille, M., Piette, J. C., Cacoub, P., Klatzmann, D. (2004) CD4+CD25+ regulatory T-cell deficiency in patients with hepatitis C-mixed cryoglobulinemia vasculitis. Blood 103, 3428-3430.
37. Alatrakchi, N., Graham, C. S., van der Vliet, H. J., Sherman, K. E., Exley, M. A., Koziel, M. J. (2007) Hepatitis C virus (HCV)-specific CD8+ cells produce transforming growth factor β that can suppress HCV-specific T-cell responses. J. Virol. 81, 5882-5892.
38. Ebinuma, H., Nakamoto, N., Li, Y., Price, D. A., Gostick, E., Levine, B. L., Tobias, J., Kwok, W. W., Chang, K. M. (2008) Identification and in-vitro expansion of functional antigen-specific CD25+FoxP3+ regulatory T-cells in hepatitis C virus infection. J. Virol. 82, 5043-5053.
39. Raimondi, G., Turner, M. S., Thomson, A. W., Morel, P. A. (2007) Naturally occurring regulatory T cells: recent insights in health and disease. Crit. Rev. Immunol. 27, 61-95.
40. Gavin, M. A., Torgerson, T. R., Houston, E., DeRoos, P., Ho, W. Y., Stray-Pedersen, A., Ocheltree, E. L., Greenberg, P. D., Ochs, H. D., Rudensky, A. Y. (2006) Single-cell analysis of normal and FOXP3-mutant human T cells: FOXP3 expression without regulatory T cell development. Proc. Natl. Acad. Sci. USA 103, 6659-6664.
41. Roncarolo, M. G., Gregori, S., Battaglia, M., Bacchetta, R., Fleischhauer, K., Levings, M. K. (2006) Interleukin-10-secreting type 1 regulatory T cells in rodents and humans. Immunol. Rev. 212, 28-50.
42. MacDonald, A. J., Duffy, M., Brady, M. T., McKiernan, S., Hall, W., Hegarty, J., Curry, M., Mills, K. H. (2002) CD4 T helper type 1 and regulatory T cells induced against the same epitopes on the core protein in hepatitis C virus-infected persons. J. Infect. Dis. 185, 720-727.
43. Tang, Q., Boden, E. K., Henriksen, K. J., Bour-Jordan, H., Bi, M., Bluestone, J. A. (2004) Distinct roles of CTLA-4 and TGF-β in CD4+CD25+ regulatory T cell function. Eur. J. Immunol. 34, 2996-3005.
44. Shapiro, S., Gershtein, V., Elias, N., Zuckerman, E., Salman, N., Lahat, N. (1998) mRNA cytokine profile in peripheral blood cells from chronic hepatitis C virus (HCV)-infected patients: effects of interferon-α (IFN-α) treatment. Clin. Exp. Immunol. 114, 55-60.
45. Kimball, P., Elswick, R. K., Shiffman, M. (2001) Ethnicity and cytokine production gauge response of patients with hepatitis C to interferon-α therapy. J. Med. Virol. 65, 510-516.
46. Taams, L. S., Akbar, A. N. (2005) Peripheral generation and function of CD4+CD25+ regulatory T cells. Curr. Top. Microbiol. Immunol. 293, 115-131.
47. Wang, J., Ioan-Facsinay, A., van der Voort, E. I., Huizinga, T. W., Toes, R. E. (2007) Transient expression of FOXP3 in human activated nonregulatory CD4+ T cells. Eur. J. Immunol. 37, 129-138.
48. Chatenoud, L., Bach, J. F. (2006) Adaptive human regulatory T cells: myth or reality? J. Clin. Invest. 116, 2325-2327.
49. Gruener, N. H., Lechner, F., Jung, M. C., Diepolder, H., Gerlach, T., Lauer, G., Walker, B., Sullivan, J., Phillips, R., Pape, G. R., Klenerman, P. (2001) Sustained dysfunction of antiviral CD8+ T lymphocytes after infection with hepatitis C virus. J. Virol. 75, 5550-5558.
50. Wedemeyer, H., He, X. S., Nascimbeni, M., Davis, A. R., Greenberg, H. B., Hoofnagle, J. H., Liang, T. J., Alter, H., Rehermann, B. (2002) Impaired effector function of hepatitis C virus-specific CD8+ T cells in chronic hepatitis C virus infection. J. Immunol. 169, 3447-3458.
51. Accapezzato, D., Francavilla, V., Paroli, M., Casciaro, M., Chircu, L. V., Cividini, A., Abrignani, S., Mondelli, M. U., Barnaba, V. (2004) Hepatic expansion of a virus-specific regulatory CD8(+) T cell population in chronic hepatitis C virus infection. J. Clin. Invest. 113, 963-972.
52. Billerbeck, E., Blum, H. E., Thimme, R. (2007) Parallel expansion of human virus-specific FoxP3- effector memory and de novo-generated FoxP3+ regulatory CD8+ T cells upon antigen recognition in vitro. J. Immunol. 179, 1039-1048.
53. Shimizu, J., Yamazaki, S., Takahashi, T., Ishida, Y., Sakaguchi, S. (2002) Stimulation of CD25(+)CD4(+) regulatory T cells through GITR breaks immunological self-tolerance. Nat. Immunol. 3, 135-142.
54. McHugh, R. S., Whitters, M. J., Piccirillo, C. A., Young, D. A., Shevach, E. M., Collins, M., Byrne, M. C. (2002) CD4(+)CD25(+) immunoregulatory T cells: gene expression analysis reveals a functional role for the glucocorticoid- induced TNF receptor. Immunity 16, 311-323.
55. Valzasina, B., Guiducci, C., Dislich, H., Killeen, N., Weinberg, A. D., Colombo, M. P. (2005) Triggering of OX40 (CD134) on CD4(+)CD25+ T cells blocks their inhibitory activity: a novel regulatory role for OX40 and its comparison with GITR. Blood 105, 2845-2851.
56. Radziewicz, H., Ibegbu, C. C., Fernandez, M. L., Workowski, K. A., Obideen, K., Wehbi, M., Hanson, H. L., Steinberg, J. P., Masopust, D., Wherry, E. J., Altman, J. D., Rouse, B. T., Freeman, G. J., Ahmed, R., Grakoui, A. (2007) Liver-infiltrating lymphocytes in chronic human hepatitis C virus infection display an exhausted phenotype with high levels of PD-1 and low levels of CD127 expression. J. Virol. 81, 2545-2553.
57. Urbani, S., Amadei, B., Tola, D., Massari, M., Schivazappa, S., Missale, G., Ferrari, C. (2006) PD-1 expression in acute hepatitis C virus (HCV) infection is associated with HCV-specific CD8 exhaustion. J. Virol. 80, 11398-11403.
58. Bopp, T., Becker, C., Klein, M., Klein-Hessling, S., Palmetshofer, A., Serfling, E., Heib, V., Becker, M., Kubach, J., Schmitt, S., Stoll, S., Schild, H., Staege, M. S., Stassen, M., Jonuleit, H., Schmitt, E. (2007) Cyclic adenosine monophosphate is a key component of regulatory T cell-mediated suppression. J. Exp. Med. 204, 1303-1310.
59. Picca, C. C., Larkin III, J., Boesteanu, A., Lerman, M. A., Rankin, A. L., Caton, A. J. (2006) Role of TCR specificity in CD4+ CD25+ regulatory T-cell selection. Immunol. Rev. 212, 74-85.
60. Tuovinen, H., Salminen, J. T., Arstila, T. P. (2006) Most human thymic and peripheral-blood CD4+ CD25+ regulatory T cells express 2 T-cell receptors. Blood 108, 4063-4070.
61. Elliott, J. I., Altmann, D. M. (1995) Dual T cell receptor α chain T cells in autoimmunity. J. Exp. Med. 182, 953-959.
62. Tang, Q., Henriksen, K. J., Boden, E. K., Tooley, A. J., Ye, J., Subudhi, S. K., Zheng, X. X., Strom, T. B., Bluestone, J. A. (2003) Cutting edge: CD28 controls peripheral homeostasis of CD4+CD25+ regulatory T cells. J. Immunol. 171, 3348-3352.
63. Kumanogoh, A., Wang, X., Lee, I., Watanabe, C., Kamanaka, M., Shi, W., Yoshida, K., Sato, T., Habu, S., Itoh, M., Sakaguchi, N., Sakaguchi, S., Kikutani, H. (2001) Increased T cell autoreactivity in the absence of CD40-CD40 ligand interactions: a role of CD40 in regulatory T cell development. J. Immunol. 166, 353-360.
64. Sutmuller, R. P., den Brok, M. H., Kramer, M., Bennink, E. J., Toonen, L. W., Kullberg, B. J., Joosten, L. A., Akira, S., Netea, M. G., Adema, G. J. (2006) Toll-like receptor 2 controls expansion and function of regulatory T cells. J. Clin. Invest. 116, 485-494.
65. Caramalho, I., Lopes-Carvalho, T., Ostler, D., Zelenay, S., Haury, M., Demengeot, J. (2003) Regulatory T cells selectively express Toll-like receptors and are activated by lipopolysaccharide. J. Exp. Med. 197, 403-411.
66. Kabelitz, D. (2007) Expression and function of Toll-like receptors in T lymphocytes. Curr. Opin. Immunol. 19, 39-45.
67. Langhans, B., Braunschweiger, I., Nischalke, H. D., Nattermann, J., Sauerbruch, T., Spengler, U. (2006) Presentation of the HCV-derived lipopeptide LP20-44 by dendritic cells enhances function of in vitro-generated CD4+ T cells via up-regulation of TLR2. Vaccine 24, 3066-3075.
68. Dolganiuc, A., Oak, S., Kodys, K., Golenbock, D. T., Finberg, R. W., Kurt-Jones, E., Szabo, G. (2004) Hepatitis C core and nonstructural 3 proteins trigger Toll-like receptor 2-mediated pathways and inflammatory activation. Gastroenterology 127, 1513-1524.
69. Hamdi, H., Godot, V., Maillot, M. C., Prejean, M. V., Cohen, N., Krzysiek, R., Lemoine, F. M., Zou, W., Emilie, D. (2007) Induction of antigen-specific regulatory T lymphocytes by human dendritic cells expressing the glucocorticoid-induced leucine zipper. Blood 110, 211-219.
70. Mennechet, F. J., Uzé, G. (2006) Interferon-λ-treated dendritic cells specifically induce proliferation of FOXP3-expressing suppressor T cells. Blood 107, 4417-4423.
71. Sharma, M. D., Baban, B., Chandler, P., Hou, D. Y., Singh, N., Yagita, H., Azuma, M., Blazar, B. R., Mellor, A. L., Munn, D. H. (2007) Plasmacytoid dendritic cells from mouse tumor-draining lymph nodes directly activate mature Tregs via indoleamine 2,3-dioxygenase. J. Clin. Invest. 117, 2570-2582.
72. Kubo, T., Hatton, R. D., Oliver, J., Liu, X., Elson, C. O., Weaver, C. T. (2004) Regulatory T cell suppression and anergy are differentially regulated by proinflammatory cytokines produced by TLR-activated dendritic cells. J. Immunol. 173, 7249-7258.
73. Pasare, C., Medzhitov, R. (2003) Toll pathway-dependent blockade of CD4+CD25+ T cell-mediated suppression by dendritic cells. Science 299, 1033-1036.
74. Waggoner, S. N., Hall, C. H., Hahn, Y. S. (2007) HCV core protein interaction with gC1q receptor inhibits Th1 differentiation of CD4+ T cells via suppression of dendritic cell IL-12 production. J. Leukoc. Biol. 82, 1407-1419.
75. Larrea, E., Riezu-Boj, J. I., Gil-Guerrero, L., Casares, N., Aldabe, R., Sarobe, P., Civeira, M. P., Heeney, J. L., Rollier, C., Verstrepen, B., Wakita, T., Borrás-Cuesta, F., Lasarte, J. J., Prieto, J. (2007) Upregulation of indoleamine 2,3-dioxygenase in hepatitis C virus infection. J. Virol. 81, 3662-3666.
76. Urbani, S., Amadei, B., Tola, D., Massari, M., Schivazappa, S., Missale, G., Ferrari, C. (2006) PD-1 expression in acute hepatitis C virus (HCV) infection is associated with HCV-specific CD8 exhaustion. J. Virol. 80, 11398-11403.
77. Bowen, D. G., Shoukry, N. H., Grakoui, A., Fuller, M. J., Cawthon, A. G., Dong, C., Hasselschwert, D. L., Brasky, K. M., Freeman, G. J., Seth, N. P., Wucherpfennig, K. W., Houghton, M., Walker, C. M.. (2008) Variable patterns of programmed death-1 (PD-1) expression on fully functional memory T cells following spontaneous resolution of hepatitis C virus infection. J. Virol. 82, 5109-5114.
78. Yao, Z. Q., King, E., Prayther, D., Yin, D., Moorman, J. (2007) T cell dysfunction by hepatitis C virus core protein involves PD-1/PDL-1 signaling. Viral Immunol. 20, 276-287.
79. Jeong, H. Y., Lee, Y. J., Seo, S. K., Lee, S. W., Park, S. J., Lee, J. N., Sohn, H. S., Yao, S., Chen, L., Choi, I. (2008) Blocking of monocyte-associated B7-H1 (CD274) enhances HCV-specific T cell immunity in chronic hepatitis C infection. J. Leukoc. Biol. 83, 755-764.
80. Belkaid, Y. (2007) Regulatory T cells and infection: a dangerous necessity. Nat. Rev. Immunol. 7, 875-888.
81. El-Serag, H. B., Anand, B., Richardson, P., Rabeneck, L. (2003) Association between hepatitis C infection and other infectious diseases: a case for targeted screening? Am. J. Gastroenterol. 98, 167-174.
82. Belkaid, Y., Piccirillo, C. A., Mendez, S., Shevach, E. M., Sacks, D. L. (2002) CD4+CD25+ regulatory T cells control Leishmania major persistence and immunity. Nature 420, 502-507.
83. Ward, S. M., Fox, B. C., Brown, P. J., Worthington, J., Fox, S. B., Chapman, R. W., Fleming, K. A., Banham, A. H., Klenerman, P. (2007) Quantification and localization of FOXP3 T lymphocytes and relation to hepatic inflammation during chronic HCV infection. J. Hepatol. 47, 316-324.
84. Kobayashi, N., Hiraoka, N., Yamagami, W., Ojima, H., Kanai, Y., Kosuge, T., Nakajima, A., Hirohashi, S. (2007) FOXP3+ regulatory T cells affect the development and progression of hepatocarcinogenesis. Clin. Cancer Res. 13, 902-911.
85. Mahnke, K., Schönfeld, K., Fondel, S., Ring, S., Karakhanova, S., Wiedemeyer, K., Bedke, T., Johnson, T. S., Storn, V., Schallenberg, S., Enk, A. H. (2007) Depletion of CD4+CD25+ human regulatory T cells in vivo: kinetics of Treg depletion and alterations in immune functions in vivo and in vitro. Int. J. Cancer 120, 2723-2733.
86. Campbell, D. J., Ziegler, S. F. (2007) FOXP3 modifies the phenotypic and functional properties of regulatory T cells. Nat. Rev. Immunol. 7, 305-310.
87. Barthlott, T., Moncrieffe, H., Veldhoen, M., Atkins, C. J., Christensen, J., O'Garra, A., Stockinger, B. (2005) CD25+ CD4+ T cells compete with naive CD4+ T cells for IL-2 and exploit it for the induction of IL-10 production. Int. Immunol. 17, 279-288.
88. Veldhoen, M., Moncrieffe, H., Hocking, R. J., Atkins, C. J., Stockinger, B. (2006) Modulation of dendritic cell function by naive and regulatory CD4+ T cells. J. Immunol. 176, 6202-6210.
89. Houot, R., Perrot, I., Garcia, E., Durand, I., Lebecque, S. (2006) Human CD4+CD25high regulatory T cells modulate myeloid but not plasmacytoid dendritic cells activation. J. Immunol. 176, 5293-5298.
90. Tadokoro, C. E., Shakhar, G., Shen, S., Ding, Y., Lino, A. C., Maraver, A., Lafaille, J. J., Dustin, M. L. (2006) Regulatory T cells inhibit stable contacts between CD4+ T cells and dendritic cells in vivo. J. Exp. Med. 203, 505-511.
91. Taams, L. S., van Amelsfort, J. M., Tiemessen, M. M., Jacobs, K. M., de Jong, E. C., Akbar, A. N., Bijlsma, J. W., Lafeber, F. P. (2005) Modulation of monocyte/macrophage function by human CD4+CD25+ regulatory T cells. Hum. Immunol. 66, 222-230.
92. Tiemessen, M. M., Jagger, A. L., Evans, H. G., van Herwijnen, M. J., John, S., Taams, L. S. (2007) CD4+CD25+Foxp3+ regulatory T cells induce alternative activation of human monocytes/macrophages. Proc. Natl. Acad. Sci. USA 104, 19446-19451.
93. Burgio, V. L., Ballardini, G., Artini, M., Caratozzolo, M., Bianchi, F. B., Levrero, M. (1998) Expression of co-stimulatory molecules by Kupffer cells in chronic hepatitis of hepatitis C virus etiology. Hepatology 27, 1600-1606.