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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 楊宏志(Hung-Chih Yang) | |
dc.contributor.author | Chia-Wen Lu | en |
dc.contributor.author | 呂佳雯 | zh_TW |
dc.date.accessioned | 2021-06-15T12:34:53Z | - |
dc.date.available | 2018-08-26 | |
dc.date.copyright | 2016-08-26 | |
dc.date.issued | 2016 | |
dc.date.submitted | 2016-08-01 | |
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Iwasaki, Inflammasomes as mediators of immunity against influenza virus. Trends Immunol, 2011. 32(1): p. 34-41. 28. Ben-Sasson, S.Z., et al., IL-1 acts directly on CD4 T cells to enhance their antigen-driven expansion and differentiation. Proc Natl Acad Sci U S A, 2009. 106(17): p. 7119-24. 29. Ben-Sasson, S.Z., et al., IL-1 enhances expansion, effector function, tissue localization, and memory response of antigen-specific CD8 T cells. J Exp Med, 2013. 210(3): p. 491-502. 30. Pang, I.K., T. Ichinohe, and A. Iwasaki, IL-1R signaling in dendritic cells replaces pattern-recognition receptors in promoting CD8(+) T cell responses to influenza A virus. Nat Immunol, 2013. 14(3): p. 246-53. 31. Schmitz, N., et al., Interleukin-1 is responsible for acute lung immunopathology but increases survival of respiratory influenza virus infection. J Virol, 2005. 79(10): p. 6441-8. 32. 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Mayer, C.T., et al., Advantages of Foxp3(+) regulatory T cell depletion using DEREG mice. Immun Inflamm Dis, 2014. 2(3): p. 162-5. 44. Lahl, K. and T. Sparwasser, In vivo depletion of FoxP3+ Tregs using the DEREG mouse model. Methods Mol Biol, 2011. 707: p. 157-72. 45. Christiaansen, A.F., P.M. Boggiatto, and S.M. Varga, Limitations of Foxp3(+) Treg depletion following viral infection in DEREG mice. J Immunol Methods, 2014. 406: p. 58-65. 46. Arvey, A., et al., Inflammation-induced repression of chromatin bound by the transcription factor Foxp3 in regulatory T cells. Nat Immunol, 2014. 15(6): p. 580-587. 47. Basu, R., et al., IL-1 signaling modulates activation of STAT transcription factors to antagonize retinoic acid signaling and control the TH17 cell-iTreg cell balance. Nat Immunol, 2015. 16(3): p. 286-95. 48. Itoh, M., et al., Thymus and Autoimmunity: Production of CD25+CD4+ Naturally Anergic and Suppressive T Cells as a Key Function of the Thymus in Maintaining Immunologic Self-Tolerance. J Immunol, 1999. 162(9): p. 5317-5326. 49. Takahashi, T., et al., Immunologic self-tolerance maintained by CD25+CD4+ naturally anergic and suppressive T cells: induction of autoimmune disease by breaking their anergic/suppressive state. Int Immunol, 1998. 10(12): p. 1969-80. 50. Collison, L.W. and D.A. Vignali, In vitro Treg suppression assays. Methods Mol Biol, 2011. 707: p. 21-37. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/50281 | - |
dc.description.abstract | 現今施打流行性感冒疫苗所產生的保護性抗體,並無法有效抵抗因抗原漂變或移型所形成的廣泛流感病毒株。而此現象有時會造成區域或全球性流感大流行的發生。然而相對於B細胞所產生的抗體,T細胞因為能辨認流感病毒共有且變異性小的胜肽片段,所以可以有效抵抗廣泛流感病毒株。除此之外,最近研究也指出,組織長駐型記憶T細胞能發出防禦警訊並提供第一線保護。因此,在T細胞疫苗發展研究中,探討哪些因子能促進建立精良的T細胞免疫,特別是在建立組織長駐型記憶T細胞的部分,顯得格外重要。在本篇研究當中,我們將會驗證由先前實驗室觀察而推論出的假說。我們認為介白素-1會經由調控調節性T細胞而阻礙組織長駐型記憶T細胞的生成。而此假說嘗試解釋先前實驗中,介白素-1接受器缺陷鼠有較多組織長駐型記憶T細胞和調節型T細胞,並較能抵抗二次流感病毒感染的現象。在本篇研究中,藉由感染前和感染期間施打白喉毒素的方式,將DEREG小鼠全身的調節型T細胞移除後,我們在感染後第28天觀察到小鼠肺部組織長駐型記憶T細胞組成下降。此觀察現象說明了調節型T細胞具有幫助組織長駐型記憶T細胞建立的特性。同時,介白素-1接受器缺陷的DEREG小鼠以相同策略去除全身的調節性T細胞後,在感染後第28天,其組織長駐型記憶T細胞在肺部的組成比例會與控制組相同,說明了介白素-1會經由調控調節型T細胞而阻礙組織長駐型記憶T細胞的生成。此外,我們也探討介白素-1對於調節型T細胞的影響。藉由未活化的T細胞在感染時受刺激生成能辨認特異抗原的調節型T細胞實驗中,我們觀察到不論介白素-1是直接或間接作用於T細胞,對於能辨認特異抗原的調節型T細胞在感染第7天與第14天的生成並沒有明顯差異。這個現象說明,介白素-1對於調節型T細胞在流感時的早期生成並不是最主要的影響因子。本篇研究主要發現,介白素-1對於組織長駐型記憶T細胞在流感時生成的影響,可能來自於介白素-1對於調節型T細胞的作用。 | zh_TW |
dc.description.abstract | Current inactivated influenza vaccine strategy fails to generate protective antibody to neutralize mutated or heterosubtypic influenza viruses caused by antigenic drift or shift, which sometimes leads to endemic and pandemic burst. In contrast, T cells can recognize conserved viral peptides and thus provide broad cross-protection against heterosubtypic and variant influenza virus. In addition, recent studies have shown that tissue-resident memory T cells (Trm) can serve as an alarm to provide the first-line defense. Thus, studying factors contributing to build up robust T cell immunity, particularly Trm, is critical for development of T cell vaccine. In this study, we examined the hypothesis inferred from our previous observation that IL-1 signaling might suppress the establishment of Trm through modulating regulatory T cells (Treg) and result in interleukin-1 receptor 1 (IL-1R1) deficient mice harboring more Trm and Treg in lung and being more resistant to secondarily heterosubtypic influenza viral infection. By systemic depletion of Treg in DEREG mice with diphtheria toxin (DT) injection prior to and during HKx31 (H3N2) challenge, we observed that the population of Trm decreased in lung at 28 days post-influenza-infection, suggesting that Treg helps establish Trm. Furthermore, depletion of Treg by DT treatment in IL-1R1-/-DEREG mice and DEREG mice harbored a similar level of Trm. This indicated that IL-1 signaling might influence the establishment of Trm through modulating Treg. We also gauged the effects of IL-1 signaling on T cells, either through IL-1 receptor on T cells or through other cells, during influenza A virus infection. Subtle differences of antigen-specific Treg induction were observed at 7 or 14 days post-infection. This observation might indicate that IL-1 signaling might not be the most important factor to induce antigen-specific Treg production during acute influenza A virus infection. We demonstrated Treg would be a possible factor for IL-1R1-deficient mice in building up better Trm. Observations in this study might lead us to unveil the enigma of virus and host interactions and also provide the mechanistic insight into building up optimal T cell vaccine. | en |
dc.description.provenance | Made available in DSpace on 2021-06-15T12:34:53Z (GMT). No. of bitstreams: 1 ntu-105-R03445113-1.pdf: 5300114 bytes, checksum: a7a7e4ec44c86e01628fa9796f856715 (MD5) Previous issue date: 2016 | en |
dc.description.tableofcontents | 口試委員會審定書(i)
誌謝(ii) 中文摘要(iv) Abstract(v) Chapter 1: Introduction 1.1 Influenza A virus (1) 1.2 T cell immunity against influenza A virus (2) 1.3 Tissue resident memory T cells (2) 1.4 Regulatory T cells (4) 1.5 Interleukin-1 (6) 1.6 Preliminary data (8) Chapter 2 : Specific aim (9) Chapter 3 : Materials and methods 3.1 Materials (11) A. Medium and buffers B. Antibodies for flow cytometry C. Antibodies for suppression assay D.Unnicked diphtheria toxin (DT) E. Anesthetic 3.2 Cell (14) 3.3 Mice (14) 3.4 Viruses (16) 3.5 Plaque assay (16) 3.6 Intranasal infection (17) 3.7 Intratracheal instillation (17) 3.8 Murine tail vein injection (17) 3.9 Regulatory T cells depletion (18) 3.10In vivo staining (18) 3.11 lung perfusion (18) 3.12 Adoptive transfer of OVA323-339-specific CD25-Foxp3-CD4+T cells (19) 3.13 CFSE labeling (19) 3.14 Suppression assay (20) 3.15 Vaccination (21) 3.16 Tissue harvesting and cells prepared for flow cytometry (22) Chapter 4 : Results 4.1 Diphtheria toxin could deplete Treg population in DEREG mice by intratracheal instillation as well as by intraperitoneal injection (24) 4.2 Regulatory T cells helped the establishment of tissue-r esident memory T cells in lung (25) 4.3 Treg might not help the establishment of Trm in lung during the resolution phase (26) 4.4 IL-1 signaling hindered the development of Trm through modulating Treg (27) 4.5 IL-1 signaling might not be critical for antigen-specific Treg induction during influenza A virus infection (28) 4.6 Building up in vitro and in vivo suppression assay systems (29) Chapter 5 : Discussion 5.1 An overview of previous studies related to this study (31) 5.2 Accomplishments of goals presented in chapter 2 of this study (32) 5.3 DT instillation through tracheal tract could not achieve specific pulmonary Treg depletion (33) 5.4 Inflammation and unwanted side effects caused by DT injection increased challenges in experiments (33) 5.5 The role of IL-1 signaling to Treg remains unclear (33) 5.6 Difficulties we encountered for building up in vitro suppression assay (36) 5.7 Conclusion (37) Chapter 6 : Figures (39) Chapter 7 : References (52) | |
dc.language.iso | en | |
dc.title | 調節性T細胞與介白素-1在A型流行性感冒病毒感染中生成組織長駐型記憶T細胞的角色 | zh_TW |
dc.title | The role of regulatory T cells and interleukin-1 signaling in development of tissue-resident memory T cells during influenza A virus infection | en |
dc.type | Thesis | |
dc.date.schoolyear | 104-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 賈景山(Jean-San Chia),顧家綺(Chia-Chi Ku),陳俊任(Chun-Jen Chen) | |
dc.subject.keyword | 組織長駐型記憶T細胞,節型T細胞,介白素-1,流感病毒, | zh_TW |
dc.subject.keyword | tissue-resident T cells,regulatory T cells,interleukin-1,influenza virus, | en |
dc.relation.page | 55 | |
dc.identifier.doi | 10.6342/NTU201601719 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2016-08-01 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 微生物學研究所 | zh_TW |
顯示於系所單位: | 微生物學科所 |
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