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  1. NTU Theses and Dissertations Repository
  2. 醫學院
  3. 免疫學研究所
請用此 Handle URI 來引用此文件: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/35087
完整後設資料紀錄
DC 欄位值語言
dc.contributor.advisor孔祥智
dc.contributor.authorTzu-Lin Yehen
dc.contributor.author葉子菱zh_TW
dc.date.accessioned2021-06-13T06:40:35Z-
dc.date.available2010-08-04
dc.date.copyright2005-08-04
dc.date.issued2005
dc.date.submitted2005-08-01
dc.identifier.citationBachmann, M. F., Barner, M., Viola, A., and Kopf, M. (1999). Distinct kinetics of cytokine production and cytolysis in effector and memory T cells after viral infection. Eur J Immunol 29, 291-299.
Bertram, E. M., Lau, P., and Watts, T. H. (2002). Temporal segregation of 4-1BB versus CD28-mediated costimulation: 4-1BB ligand influences T cell numbers late in the primary response and regulates the size of the T cell memory response following influenza infection. J Immunol 168, 3777-3785.
Blotta, M. H., Marshall, J. D., DeKruyff, R. H., and Umetsu, D. T. (1996). Cross-linking of the CD40 ligand on human CD4+ T lymphocytes generates a costimulatory signal that up-regulates IL-4 synthesis. J Immunol 156, 3133-3140.
Borst, J., Hendriks, J., and Xiao, Y. (2005). CD27 and CD70 in T cell and B cell activation. Curr Opin Immunol 17, 275-281.
Bourgeois, C., Rocha, B., and Tanchot, C. (2002). A role for CD40 expression on CD8+ T cells in the generation of CD8+ T cell memory. Science 297, 2060-2063.
Brenner, B., Koppenhoefer, U., Grassme, H., Kun, J., Lang, F., and Gulbins, E. (1997). Evidence for a novel function of the CD40 ligand as a signalling molecule in T-lymphocytes. FEBS Lett 417, 301-306.
Chambers, C. A., and Allison, J. P. (1997). Co-stimulation in T cell responses. Curr Opin Immunol 9, 396-404.
Chang, J. F., Thomas, C. A., 3rd, and Kung, J. T. (1991). Induction of high level IL-2 production in CD4+8- T helper lymphocytes requires post-thymic development. J Immunol 147, 851-859.
Chen, F. L., and Kung, J. T. (1996). Deficient CD4+ T cell proliferation in the class 1 MHC-restricted 2C TCR-transgenic mouse. J Immunol 156, 2036-2044.

Croft, M., Bradley, L. M., and Swain, S. L. (1994). Naive versus memory CD4 T cell response to antigen. Memory cells are less dependent on accessory cell costimulation and can respond to many antigen-presenting cell types including resting B cells. J Immunol 152, 2675-2685.
Del Prete, G., De Carli, M., D'Elios, M. M., Daniel, K. C., Almerigogna, F., Alderson, M., Smith, C. A., Thomas, E., and Romagnani, S. (1995). CD30-mediated signaling promotes the development of human T helper type 2-like T cells. J Exp Med 182, 1655-1661.
Evans, D. E., Prell, R. A., Thalhofer, C. J., Hurwitz, A. A., and Weinberg, A. D. (2001). Engagement of OX40 enhances antigen-specific CD4(+) T cell mobilization/memory development and humoral immunity: comparison of alphaOX-40 with alphaCTLA-4. J Immunol 167, 6804-6811.
Futagawa, T., Akiba, H., Kodama, T., Takeda, K., Hosoda, Y., Yagita, H., and Okumura, K. (2002). Expression and function of 4-1BB and 4-1BB ligand on murine dendritic cells. Int Immunol 14, 275-286.
Gascan, H., Gauchat, J. F., Aversa, G., Van Vlasselaer, P., and de Vries, J. E. (1991). Anti-CD40 monoclonal antibodies or CD4+ T cell clones and IL-4 induce IgG4 and IgE switching in purified human B cells via different signaling pathways. J Immunol 147, 8-13.
Gimmi, C. D., Freeman, G. J., Gribben, J. G., Gray, G., and Nadler, L. M. (1993). Human T-cell clonal anergy is induced by antigen presentation in the absence of B7 costimulation. Proc Natl Acad Sci U S A 90, 6586-6590.
Grakoui, A., Bromley, S. K., Sumen, C., Davis, M. M., Shaw, A. S., Allen, P. M., and Dustin, M. L. (1999). The immunological synapse: a molecular machine controlling T cell activation. Science 285, 221-227.
Hendriks, J., Gravestein, L. A., Tesselaar, K., van Lier, R. A., Schumacher, T. N., and Borst, J. (2000). CD27 is required for generation and long-term maintenance of T cell immunity. Nat Immunol 1, 433-440.

Hintzen, R. Q., Lens, S. M., Beckmann, M. P., Goodwin, R. G., Lynch, D., and van Lier, R. A. (1994). Characterization of the human CD27 ligand, a novel member of the TNF gene family. J Immunol 152, 1762-1773.
Huang, L. R., Chen, F. L., Chen, Y. T., Lin, Y. M., and Kung, J. T. (2000). Potent induction of long-term CD8+ T cell memory by short-term IL-4 exposure during T cell receptor stimulation. Proc Natl Acad Sci U S A 97, 3406-3411.
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.
Kelly, J. M., Darcy, P. K., Markby, J. L., Godfrey, D. I., Takeda, K., Yagita, H., and Smyth, M. J. (2002). Induction of tumor-specific T cell memory by NK cell-mediated tumor rejection. Nat Immunol 3, 83-90.
Khayyamian, S., Hutloff, A., Buchner, K., Grafe, M., Henn, V., Kroczek, R. A., and Mages, H. W. (2002). ICOS-ligand, expressed on human endothelial cells, costimulates Th1 and Th2 cytokine secretion by memory CD4+ T cells. Proc Natl Acad Sci U S A 99, 6198-6203.
Kim, J., Choi, S. P., La, S., Seo, J. S., Kim, K. K., Nam, S. H., and Kwon, B. (2003). Constitutive expression of 4-1BB on T cells enhances CD4+ T cell responses. Exp Mol Med 35, 509-517.
Kim, M. Y., Bekiaris, V., McConnell, F. M., Gaspal, F. M., Raykundalia, C., and Lane, P. J. (2005). OX40 signals during priming on dendritic cells inhibit CD4 T cell proliferation: IL-4 switches off OX40 signals enabling rapid proliferation of Th2 effectors. J Immunol 174, 1433-1437.
Koppenhoefer, U., Brenner, B., Lang, F., and Gulbins, E. (1997). The CD40-ligand stimulates T-lymphocytes via the neutral sphingomyelinase: a novel function of the CD40-ligand as signalling molecule. FEBS Lett 414, 444-448.
Lee, H. W., Nam, K. O., Seo, S. K., Kim, Y. H., Kang, H., and Kwon, B. S. (2003). 4-1BB cross-linking enhances the survival and cell cycle progression of CD4 T lymphocytes. Cell Immunol 223, 143-150.
Lenschow, D. J., Walunas, T. L., and Bluestone, J. A. (1996). CD28/B7 system of T cell costimulation. Annu Rev Immunol 14, 233-258.
Lenz, D. C., Kurz, S. K., Lemmens, E., Schoenberger, S. P., Sprent, J., Oldstone, M. B., and Homann, D. (2004). IL-7 regulates basal homeostatic proliferation of antiviral CD4+T cell memory. Proc Natl Acad Sci U S A 101, 9357-9362.
Liu, Y., Jones, B., Brady, W., Janeway, C. A., Jr., and Linsley, P. S. (1992). Co-stimulation of murine CD4 T cell growth: cooperation between B7 and heat-stable antigen. Eur J Immunol 22, 2855-2859.
Liu, Y., Wenger, R. H., Zhao, M., and Nielsen, P. J. (1997). Distinct costimulatory molecules are required for the induction of effector and memory cytotoxic T lymphocytes. J Exp Med 185, 251-262.
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.
Ohshima, Y., Tanaka, Y., Tozawa, H., Takahashi, Y., Maliszewski, C., and Delespesse, G. (1997). Expression and function of OX40 ligand on human dendritic cells. J Immunol 159, 3838-3848.
Okamoto, N., Nukada, Y., Tezuka, K., Ohashi, K., Mizuno, K., and Tsuji, T. (2004). AILIM/ICOS signaling induces T-cell migration/polarization of memory/effector T-cells. Int Immunol 16, 1515-1522.
Podack, E. R., Strbo, N., Sotosec, V., and Muta, H. (2002). CD30-governor of memory T cells? Ann N Y Acad Sci 975, 101-113.
Rogers, N. J., Jackson, I. M., Jordan, W. J., Lombardi, G., Delikouras, A., and Lechler, R. I. (2003). CD40 can costimulate human memory T cells and favors IL-10 secretion. Eur J Immunol 33, 1094-1104.
Rogers, P. R., Dubey, C., and Swain, S. L. (2000). Qualitative changes accompany memory T cell generation: faster, more effective responses at lower doses of antigen. J Immunol 164, 2338-2346.
Rogers, P. R., Song, J., Gramaglia, I., Killeen, N., and Croft, M. (2001). OX40 promotes Bcl-xL and Bcl-2 expression and is essential for long-term survival of CD4 T cells. Immunity 15, 445-455.
Seder, R. A., and Ahmed, R. (2003). Similarities and differences in CD4+ and CD8+ effector and memory T cell generation. Nat Immunol 4, 835-842.
Sprent, J., and Surh, C. D. (2002). T cell memory. Annu Rev Immunol 20, 551-579.
Suresh, M., Whitmire, J. K., Harrington, L. E., Larsen, C. P., Pearson, T. C., Altman, J. D., and Ahmed, R. (2001). Role of CD28-B7 interactions in generation and maintenance of CD8 T cell memory. J Immunol 167, 5565-5573.
Veldhoen, M., Magee, A. I., Penha-Goncalves, M. N., and Stockinger, B. (2005). Transduction of naive CD4 T cells with kinase-deficient Lck-HIV-Tat fusion protein dampens T cell activation and provokes a switch to regulatory function. Eur J Immunol 35, 207-216.
Watts, T. H., and DeBenedette, M. A. (1999). T cell co-stimulatory molecules other than CD28. Curr Opin Immunol 11, 286-293.
Whitmire, J. K., and Ahmed, R. (2000). Costimulation in antiviral immunity: differential requirements for CD4(+) and CD8(+) T cell responses. Curr Opin Immunol 12, 448-455.
Yamamoto, J., Adachi, Y., Onoue, Y., Kanegane, H., Miyawaki, T., Toyoda, M., Seki, T., and Morohashi, M. (2000). CD30 expression on circulating memory CD4+ T cells as a Th2-dominated situation in patients with atopic dermatitis. Allergy 55, 1011-1018.
Zhang, N., and He, Y. W. (2005). The antiapoptotic protein Bcl-xL is dispensable for the development of effector and memory T lymphocytes. J Immunol 174, 6967-6973.
dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/35087-
dc.description.abstract記憶型T淋巴球可抵抗對外來抗原,在免疫系統當中扮演重要的角色。 然而,對於控制記憶型CD4+ T淋巴球產生的詳細機制卻還不甚清楚。 在本研究當中,我們嘗試著去研究輔助刺激因子(costimulatory molecule)是否參與在記憶型CD4+ T淋巴球的生成。 經由cDNA的轉染(transfection)製造出表現在細胞表面帶有CD24、CD40、CD70、CD86、CD153、OX40L、4-1BBL和IcosL的EL4腫瘤細胞株。 另外,為了使這些轉染細胞株(transfectant)可以當作抗原呈現細胞(antigen-presenting cell)以活化CD4+ T淋巴球,因此在每種轉染細胞株的細胞表面上再加以轉染FcgRI,使轉染細胞株可以結合上anti-CD3單株抗體,並將之呈現給CD4+ T淋巴球以刺激之。 在活體外實驗的結果發現,除了CD28:CD86,在其他輔助型因子的刺激之下,CD4+ T淋巴球的活化狀況都不是很好。 因此在利用轉染細胞株EL4活化CD4+ T淋巴球時,我們同時加入anti-CD3和anti-CD28的刺激。 CD4+ T淋巴球在帶有各種不同輔助型刺激因子轉染細胞株EL4的刺激之後,再打入宿主老鼠體內,我們發現細胞表面表現CD40的轉染細胞株,可提供CD40:CD40L的刺激,造成大量長期存活的CD4+ T淋巴球。 另外,我們還發現CD4+ T淋巴球在B淋巴球的刺激之下再外加第四介白素也可以幫助生成長期存活的CD4+ T淋巴球。 至於其他的輔助刺激因子,包括CD28:CD86、CD27:CD70、CD30:CD153、OX40:OX40L、Icos:IcosL和4-1BB:4-1BBL,則對於記憶型CD4 T 淋巴球的生成沒有正向的影響。以上的研究發現對於腫瘤的治療與疫苗的開發皆有所幫助。zh_TW
dc.description.abstractLong-lived memory T cells play important roles in the defense against foreign invaders, although the mechanisms involved in memory T cell generation are not fully understood. In this study, I studied the effects costimulatory molecules play on memory CD4+ T cell memory generation. EL4 tumor cell lines that had through transfection been made to stably co-express FcgRI and one or combinations of CD24, CD40, CD70, CD86, CD153, OX40L, 4-1BBL, and IcosL costimulators were used as antigen-presenting cells to activate CD4+ T cells. Such transfectants delivered signal 1 through anti-CD3 mAbs presented by its FcgRI and signal 2 through the given costimulatory molecules it expresses. Except CD28:CD86, all other costimulatory molecules were ineffective at causing CD4+ T cell proliferation. To insure proper activation of CD4 T cells, anti-CD3 and anti-CD28 were both added and were presented via the FcgRI on the various costimulator-expressing EL4 transfectants. Activated CD4+ T cells were adoptively transferred into histocompatible, congenic hosts and their presence was monitored over time. CD4+ T cells activated by anti-CD3/CD28 in the context of CD40:CD154 developed long-term survival potential. In addition, CD4+ T cells activated by anti-CD3/CD28 in the context of B cells + IL-4 also developed long-term survival potential. All other costimulators, CD28:CD86, CD27:CD70, CD30:CD153, OX40:OX40L, Icos:IcosL, and 4-1BB:4-1BBL, did not have positive effects on long-term CD4 memory generation. These results may have implications in tumor therapy and vaccine development.en
dc.description.provenanceMade available in DSpace on 2021-06-13T06:40:35Z (GMT). No. of bitstreams: 1
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Previous issue date: 2005
en
dc.description.tableofcontentsTable of Contents
Abstract………………………………………………………………. v
Abstract (Chinese)…………………………………………………... vi
CHAPTER I Introduction………………………………………… 1
CHAPTER II Experimental Setup………………………..….…... 8
2.1 Mice…………….………………………………….………… 9
2.2 Isolation of spleen CD4+ T cells………………………….….. 10
2.3 RNA extraction and reverse transcription……………....……. 12
2.4 Cloning of CD24, CD40, CD153……………………………. 14
2.5 Transfection…………………………………………….……. 16
2.6 Preparation of Antigen-presenting cells (B cell blasts)…..….. 18
2.7 Activation of B10 CD4+ T cells………………………...……. 20
2.8 Adoptive transfer……………………………………….……. 21
2.9 Donor cell persistence traced by flow cytometry………..…... 22
CHAPTER III Experiment Results………………….…………... 23
3.1 Generation of EL4 lines that co-express FcgRI and different costimulatory molecules……………………………….…... 24
3.2 Using EL4 transfectants as APC to induce CD4+ T cells proliferation…………………………………………..……. 25
3.3 The effect of 4-1BBL, IcosL, CD70, and OX40L on the generation of memory CD4 T cells…………………….….. 26
3.4 The effect of IL-2 on the generation of memory CD4+ T cells ………………………………………………..…….. 27
3.5 The effect of IL-4 on the generation of long-lived T cells…… 28
3.6 The effect of combined costimulation signaling on the generation of memory CD4 T cells………………………… 29
3.7 The effect of CD40, CD153, OX40L on the generation of memory CD4+ T cells……………………………….……... 30
3.8 Rapid decline of donor T cells might be caused by rejecrion …………………………………………………. 30
3.9 Summary……………………………………………………... 31
CHAPTER IV Discussion………………….………………..……. 32
CHAPTER V Experiment Figures……………………………….. 39
REFERENCES……………………………………………………… 49
dc.language.isoen
dc.subject記憶型 CD4+ T 淋巴球zh_TW
dc.subject輔助刺激因子zh_TW
dc.subject第四介白素zh_TW
dc.subjectIL-4en
dc.subjectmemory CD4 T cellen
dc.subjectco-stimulatory moleculesen
dc.title輔助刺激因子與第四介白素在
記憶型CD4+ T 淋巴球生成中所扮演的角色
zh_TW
dc.titleRole of co-stimulatory molecules and IL-4 in the generation of long-term CD4+ T cell memoryen
dc.typeThesis
dc.date.schoolyear93-2
dc.description.degree碩士
dc.contributor.oralexamcommittee伍安怡,繆希椿
dc.subject.keyword輔助刺激因子,第四介白素,記憶型 CD4+ T 淋巴球,zh_TW
dc.subject.keywordco-stimulatory molecules,IL-4,memory CD4 T cell,en
dc.relation.page53
dc.rights.note有償授權
dc.date.accepted2005-08-01
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

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