請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/30208
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 許秉寧(Ping-Ning Hsu) | |
dc.contributor.author | Chuan Wan | en |
dc.contributor.author | 萬川 | zh_TW |
dc.date.accessioned | 2021-06-13T01:43:41Z | - |
dc.date.available | 2009-08-08 | |
dc.date.copyright | 2007-08-08 | |
dc.date.issued | 2007 | |
dc.date.submitted | 2007-07-11 | |
dc.identifier.citation | (2002). Hepatitis B. In (World Health Organization).
Agata, Y., Kawasaki, A., Nishimura, H., Ishida, Y., Tsubata, T., Yagita, H., and Honjo, T. (1996). Expression of the PD-1 antigen on the surface of stimulated mouse T and B lymphocytes. International immunology 8, 765-772. Alter, M.J. (2002). Prevention of spread of hepatitis C. Hepatology 36, S93-98. Alter, M.J., Kruszon-Moran, D., Nainan, O.V., McQuillan, G.M., Gao, F., Moyer, L.A., Kaslow, R.A., and Margolis, H.S. (1999). The prevalence of hepatitis C virus infection in the United States, 1988 through 1994. N Engl J Med 341, 556-562. Barber, D.L., Wherry, E.J., Masopust, D., Zhu, B., Allison, J.P., Sharpe, A.H., Freeman, G.J., and Ahmed, R. (2006). Restoring function in exhausted CD8 T cells during chronic viral infection. Nature 439, 682-687. Beier, K.C., Hutloff, A., Dittrich, A.M., Heuck, C., Rauch, A., Buchner, K., Ludewig, B., Ochs, H.D., Mages, H.W., and Kroczek, R.A. (2000). Induction, binding specificity and function of human ICOS. Eur J Immunol 30, 3707-3717. Blank, C., Kuball, J., Voelkl, S., Wiendl, H., Becker, B., Walter, B., Majdic, O., Gajewski, T.F., Theobald, M., Andreesen, R., and Mackensen, A. (2006). Blockade of PD-L1 (B7-H1) augments human tumor-specific T cell responses in vitro. International journal of cancer 119, 317-327. Blazar, B.R., Carreno, B.M., Panoskaltsis-Mortari, A., Carter, L., Iwai, Y., Yagita, H., Nishimura, H., and Taylor, P.A. (2003). Blockade of programmed death-1 engagement accelerates graft-versus-host disease lethality by an IFN-gamma-dependent mechanism. J Immunol 171, 1272-1277. Boettler, T., Panther, E., Bengsch, B., Nazarova, N., Spangenberg, H.C., Blum, H.E., and Thimme, R. (2006). 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 80, 3532-3540. Boisvert, J., Kunkel, E.J., Campbell, J.J., Keeffe, E.B., Butcher, E.C., and Greenberg, H.B. (2003). Liver-infiltrating lymphocytes in end-stage hepatitis C virus: subsets, activation status, and chemokine receptor phenotypes. J Hepatol 38, 67-75. Chen, L. (2004). Co-inhibitory molecules of the B7-CD28 family in the control of T-cell immunity. Nature reviews 4, 336-347. Chisari, F.V., and Ferrari, C. (1995). Hepatitis B virus immunopathogenesis. Annu Rev Immunol 13, 29-60. Cooper, S., Erickson, A.L., Adams, E.J., Kansopon, J., Weiner, A.J., Chien, D.Y., Houghton, M., Parham, P., and Walker, C.M. (1999). Analysis of a successful immune response against hepatitis C virus. Immunity 10, 439-449. Crispe, I.N. (2003). Hepatic T cells and liver tolerance. Nature reviews 3, 51-62. Day, C.L., Kaufmann, D.E., Kiepiela, P., Brown, J.A., Moodley, E.S., Reddy, S., Mackey, E.W., Miller, J.D., Leslie, A.J., DePierres, C., et al. (2006). PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression. Nature 443, 350-354. Dienstag, J.L., Schiff, E.R., Wright, T.L., Perrillo, R.P., Hann, H.W., Goodman, Z., Crowther, L., Condreay, L.D., Woessner, M., Rubin, M., and Brown, N.A. (1999). Lamivudine as initial treatment for chronic hepatitis B in the United States. N Engl J Med 341, 1256-1263. Dong, H., and Chen, L. (2003). B7-H1 pathway and its role in the evasion of tumor immunity. Journal of molecular medicine (Berlin, Germany) 81, 281-287. Dong, H., Zhu, G., Tamada, K., and Chen, L. (1999). B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nature medicine 5, 1365-1369. Freeman, G.J., Long, A.J., Iwai, Y., Bourque, K., Chernova, T., Nishimura, H., Fitz, L.J., Malenkovich, N., Okazaki, T., Byrne, M.C., et al. (2000). Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med 192, 1027-1034. Freeman, G.J., Wherry, E.J., Ahmed, R., and Sharpe, A.H. (2006). Reinvigorating exhausted HIV-specific T cells via PD-1-PD-1 ligand blockade. The Journal of experimental medicine 203, 2223-2227. Ganem, D., and Prince, A.M. (2004). Hepatitis B virus infection--natural history and clinical consequences. N Engl J Med 350, 1118-1129. Greenwald, R.J., Freeman, G.J., and Sharpe, A.H. (2005). The B7 family revisited. Annu Rev Immunol 23, 515-548. Harding, F.A., and Allison, J.P. (1993). CD28-B7 interactions allow the induction of CD8+ cytotoxic T lymphocytes in the absence of exogenous help. J Exp Med 177, 1791-1796. Heydtmann, M., Lalor, P.F., Eksteen, J.A., Hubscher, S.G., Briskin, M., and Adams, D.H. (2005). CXC chemokine ligand 16 promotes integrin-mediated adhesion of liver-infiltrating lymphocytes to cholangiocytes and hepatocytes within the inflamed human liver. J Immunol 174, 1055-1062. Hutloff, A., Dittrich, A.M., Beier, K.C., Eljaschewitsch, B., Kraft, R., Anagnostopoulos, I., and Kroczek, R.A. (1999). ICOS is an inducible T-cell co-stimulator structurally and functionally related to CD28. Nature 397, 263-266. Ishida, Y., Agata, Y., Shibahara, K., and Honjo, T. (1992). Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. The EMBO journal 11, 3887-3895. Jinlin Hou, Zhihua Liu, and Gu, F. (2005). Epidemiology and Prevention of Hepatitis B Virus Infection. Int J Med Sci 2, 50-57. Knolle, P.A., and Gerken, G. (2000). Local control of the immune response in the liver. Immunological reviews 174, 21-34. Koch, S., Solana, R., Dela Rosa, O., and Pawelec, G. (2006). Human cytomegalovirus infection and T cell immunosenescence: a mini review. Mech Ageing Dev 127, 538-543. Lechner, F., Wong, D.K., Dunbar, P.R., Chapman, R., Chung, R.T., Dohrenwend, P., Robbins, G., Phillips, R., Klenerman, P., and Walker, B.D. (2000). Analysis of successful immune responses in persons infected with hepatitis C virus. J Exp Med 191, 1499-1512. Lohr, H.F., Schlaak, J.F., Gerken, G., Fleischer, B., Dienes, H.P., and Meyer zum Buschenfelde, K.H. (1994). Phenotypical analysis and cytokine release of liver-infiltrating and peripheral blood T lymphocytes from patients with chronic hepatitis of different etiology. Liver 14, 161-166. Maier, H., Isogawa, M., Freeman, G.J., and Chisari, F.V. (2007). PD-1:PD-L1 interactions contribute to the functional suppression of virus-specific CD8+ T lymphocytes in the liver. J Immunol 178, 2714-2720. McAdam, A.J., Chang, T.T., Lumelsky, A.E., Greenfield, E.A., Boussiotis, V.A., Duke-Cohan, J.S., Chernova, T., Malenkovich, N., Jabs, C., Kuchroo, V.K., et al. (2000). Mouse inducible costimulatory molecule (ICOS) expression is enhanced by CD28 costimulation and regulates differentiation of CD4+ T cells. J Immunol 165, 5035-5040. Nishimura, H., and Honjo, T. (2001). PD-1: an inhibitory immunoreceptor involved in peripheral tolerance. Trends in immunology 22, 265-268. Nishimura, H., Nose, M., Hiai, H., Minato, N., and Honjo, T. (1999). Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Immunity 11, 141-151. Pan, C.Q., and Zhang, J.X. (2005). Natural History and Clinical Consequences of Hepatitis B Virus Infection. Int J Med Sci 2, 36-40. Pawelec, G., Koch, S., Franceschi, C., and Wikby, A. (2006). Human immunosenescence: does it have an infectious component? Ann N Y Acad Sci 1067, 56-65. Penna, A., Pilli, M., Zerbini, A., Orlandini, A., Mezzadri, S., Sacchelli, L., Missale, G., and Ferrari, C. (2007). Dysfunction and functional restoration of HCV-specific CD8 responses in chronic hepatitis C virus infection. Hepatology (Baltimore, Md 45, 588-601. Petrovas, C., Casazza, J.P., Brenchley, J.M., Price, D.A., Gostick, E., Adams, W.C., Precopio, M.L., Schacker, T., Roederer, M., Douek, D.C., and Koup, R.A. (2006). PD-1 is a regulator of virus-specific CD8+ T cell survival in HIV infection. The Journal of experimental medicine 203, 2281-2292. 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., et al. (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. Sakai, Y., Izumi, N., Marumo, F., and Sato, C. (1993). Quantitative immunohistochemical analysis of lymphocyte subsets in alcoholic liver disease. Journal of gastroenterology and hepatology 8, 39-43. Sato, T., Thorlacius, H., Johnston, B., Staton, T.L., Xiang, W., Littman, D.R., and Butcher, E.C. (2005). Role for CXCR6 in recruitment of activated CD8+ lymphocytes to inflamed liver. J Immunol 174, 277-283. Shahinian, A., Pfeffer, K., Lee, K.P., Kundig, T.M., Kishihara, K., Wakeham, A., Kawai, K., Ohashi, P.S., Thompson, C.B., and Mak, T.W. (1993). Differential T cell costimulatory requirements in CD28-deficient mice. Science 261, 609-612. Sharpe, A.H., Green, J.M., Noel, P.J., Sperling, A.I., Walunas, T.L., Gray, G.S., Bluestone, J.A., and Thompson, C.B. (1995). Analysis of lymphocyte costimulation in vivo using transgenic and 'knockout' mice Absence of B7-dependent responses in CD28-deficient mice. Curr Opin Immunol 7, 389-395. Shlapatska, L.M., Mikhalap, S.V., Berdova, A.G., Zelensky, O.M., Yun, T.J., Nichols, K.E., Clark, E.A., and Sidorenko, S.P. (2001). CD150 association with either the SH2-containing inositol phosphatase or the SH2-containing protein tyrosine phosphatase is regulated by the adaptor protein SH2D1A. J. Immunol. 166, 5480-5487. Si, L., Whiteside, T.L., Van Thiel, D.H., and Rabin, B.S. (1984). Lymphocyte subpopulations at the site of 'piecemeal' necrosis in end stage chronic liver diseases and rejecting liver allografts in cyclosporine-treated patients. Laboratory investigation; a journal of technical methods and pathology 50, 341-347. Tivol, E.A., Borriello, F., Schweitzer, A.N., Lynch, W.P., Bluestone, J.A., and Sharpe, A.H. (1995). Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4. Immunity 3, 541-547. Trautmann, L., Janbazian, L., Chomont, N., Said, E.A., Gimmig, S., Bessette, B., Boulassel, M.R., Delwart, E., Sepulveda, H., Balderas, R.S., et al. (2006). Upregulation of PD-1 expression on HIV-specific CD8+ T cells leads to reversible immune dysfunction. Nature medicine 12, 1198-1202. Ueda, H., Howson, J.M., Esposito, L., Heward, J., Snook, H., Chamberlain, G., Rainbow, D.B., Hunter, K.M., Smith, A.N., Di Genova, G., et al. (2003). Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease. Nature 423, 506-511. Urbani, S., Amadei, B., Tola, D., Massari, M., Schivazappa, S., Missale, G., and 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. Waterhouse, P., Penninger, J.M., Timms, E., Wakeham, A., Shahinian, A., Lee, K.P., Thompson, C.B., Griesser, H., and Mak, T.W. (1995). Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4. Science 270, 985-988. Wong, D.K., Cheung, A.M., O'Rourke, K., Naylor, C.D., Detsky, A.S., and Heathcote, J. (1993). Effect of alpha-interferon treatment in patients with hepatitis B e antigen-positive chronic hepatitis B. A meta-analysis. Ann Intern Med 119, 312-323. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/30208 | - |
dc.description.abstract | 肝臟的病毒感染是一個全球性的嚴重問題。全球有數以百萬計的人感染病毒性肝炎,而且其中許多人會進展成為慢性病毒性肝炎。至於造成持續地病毒感染和不良的免疫反應的病因仍待進一步地闡明。近來,一些研究揭露了共同抑制因子(co-inhibitory molecules)在減損病毒特異性淋巴球功能的重要性。而化學性激素接受器在近幾年也被發現在召集淋巴球回流至特異的器官上佔有重要的角色。
有鑑於此,首先,我們試著找出共同信號分子在周邊淋巴球和肝臟浸潤淋巴球上的表現是否有任何的不同。接著,我們試著找出這些分子之間的相關性。化學性激素接受器CXCR6,一種已知會召集淋巴球回流至發炎肝臟的分子,它們在慢性病毒性肝炎病人淋巴球上的表現量及它們和共同抑制性或共同剌激性分子間的相關性也是這次研究的目標。 在這次研究中,我們發現相較於周邊血淋巴球,肝臟浸潤淋巴球PD-1分子的表現量有顯著的增加,而CD28分子的表現量有明顯的降低。在肝臟浸潤淋巴球中,化學性激素接受器CXCR6表現量也有顯著的增加,同時在具化學性激素接受器CXCR6表現的肝臟浸潤淋巴球中,帶有PD-1分子的細胞數也有增加。此外,我們觀察到:相較於周邊血淋巴球,肝臟浸潤淋巴球的CD127表現(淋巴球的耗竭性標記),有明顯降低的現象。由以上的結果可知:相對於周邊血淋巴球,在肝臟浸潤淋巴球較高的PD-1表現和較低的CD28表現,可能暗示著慢性病毒性肝炎的肝浸潤淋巴球在功能上是受損的。另外,具化學性激素接受器CXCR6表現的肝臟浸潤淋巴球中,帶有PD-1分子的細胞數也有增加。可能暗示召集回流至發炎肝臟的淋巴球在功能上是受到抑制的。 | zh_TW |
dc.description.abstract | Viral infection in liver is a serious problem worldwide. There are millions of people infected with viral hepatitis and many of those progress to chronic virus infection of the liver. The etiology of persistent viral infection and poor immune response to clear these viruses remains for further elucidation. Recently some studies shed light on the importance of co-inhibitory molecules in compromising the function of virus specific cytotoxic T cells. Chemokine receptors also are known to play important roles in the homing of lymphocytes into the specific organs.
First, we tried to find out whether there is any difference in the expression of co-stimulatory/co-inhibitory molecules in peripheral blood lymphocytes and hepatic infiltrating lymphocytes. We then evaluated the correlation between these molecules. A chemokine receptor CXCR6, a recruiting molecule for lymphocytes to inflamed liver, was studied for its expression in chronic viral hepatitis patients and for the relationship between its expression and co-stimulatory/co-inhibitory molecules. In this study, we found that PD-1 molecule expression was increased and CD28 molecule expression was decreased in the liver infiltrating lymphocytes (LILs) compared to their expressions in the peripheral blood lymphocytes (PBLs). There is an increase of CXCR6 expression in LILs. In hepatic infiltrating lymphocytes, the number of PD-1+CXCR6+CD3+T cells is increased compared with the number of these cells in PBLs. There was a low expression level of CD127, the marker of exhausted lymphocytes, in the LILs compared to the PBLs. The higher expression of PD-1 and lower CD28 expression in liver infiltrating lymphocytes might be suggestive of the impairment of LIL function in chronic hepatitis. Besides, the number of PD-1+CXCR6+CD3+ T cells is increased in LILs. This finding may imply the recruited hepatic infiltrating lymphocytes have impaired function. | en |
dc.description.provenance | Made available in DSpace on 2021-06-13T01:43:41Z (GMT). No. of bitstreams: 1 ntu-96-R94449012-1.pdf: 563482 bytes, checksum: bde1bf21056e0047805ce57f38771cbe (MD5) Previous issue date: 2007 | en |
dc.description.tableofcontents | 謝辭……………………………………………………………………………………. iii
中文摘要…………………………………………………………………………….v 英文摘要………………………………………………………………………………..vi Chapter 1: Introduction ……………………………………………………………...1 1.1 Chronic viral hepatitis…..………………………………………………….1 1.2 Liver and hepatic infiltrating lymphocytes………………………………...4 1.3 T lymphocytes and two-signal theory……………………………………..5 1.4 Co-signaling molecules…………………………………….........................7 1.5 Lymphocytes recruitment and CXCR6…………………………………….9 Chapter 2: Material and Methods…………………………………………………...11 Chapter 3: Results…………………………………………………………………...17 Part 1: The patients……………..…………………………….………………..17 Part 2: Characterization of the hepatic infiltrating lymphocytes and hepatocytes in liver tissue specimen…….………...……………….....................17 Part 3: Phenotypes of the hepatic infiltrating lymphocytes isolated from liver tissue…………………………………..….........................................17 Part 4: The expression level of co-inhibitory and co-stimulatory molecules on hepatic infiltrating lymphocytes and on the peripheral blood lymphocytes…18 Part 5: The correlation between co-inhibitory and co-stimulatory molecules in hepatic infiltrating lymphocytes and peripheral blood lymphocytes……..18 Part 6: The correlation between co-inhibitory/co-stimulatory molecules and chemokine receptors CXCR6 in hepatic infiltrating lymphocytes and peripheral blood lymphocytes………………….……………………………… 19 Part 7: The expression level of CD127 in the hepatic infiltrating lymphocytes and peripheral blood lymphocytes…………………………………………….. 20 Part 8: The correlation between clinical data record and the expression of co-inhibitory/co-stimulatory molecules……………………………………… 20 Chapter 4: Discussion………………………………………………………………21 Reference……………………………………………………………………………30 Figures and Tables…………………………………………………..........................39 | |
dc.language.iso | en | |
dc.title | 在慢性病毒性肝炎病人肝臟浸潤細胞的共同抑制性分子和共同刺激性分子表現量之研究 | zh_TW |
dc.title | The Study of the Expression of Co-inhibitory and Co-stimulatory Molecules in Hepatic Infiltrating Lymphocytes in Chronic Viral Hepatitis | en |
dc.type | Thesis | |
dc.date.schoolyear | 95-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 謝世良(Shie-Liang Hsieh),司徒惠康(Huey-Kang Sytwu) | |
dc.subject.keyword | 周邊血細胞,肝浸潤細胞,共同抑制性分子,共同刺激性分子, | zh_TW |
dc.subject.keyword | PBLs,LILs,co-inhibitory molecules,co-stimulatory molecules, | en |
dc.relation.page | 59 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2007-07-11 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 免疫學研究所 | zh_TW |
顯示於系所單位: | 免疫學研究所 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-96-1.pdf 目前未授權公開取用 | 550.28 kB | Adobe PDF |
系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。