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DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 楊宏志(Hung-Chih Yang) | |
dc.contributor.author | Yu-Sung Hsu | en |
dc.contributor.author | 徐佑松 | zh_TW |
dc.date.accessioned | 2021-06-16T09:17:50Z | - |
dc.date.available | 2020-08-27 | |
dc.date.copyright | 2020-08-27 | |
dc.date.issued | 2020 | |
dc.date.submitted | 2020-08-15 | |
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Samira Mansouri et al. 2019. Immature lung TNFR2 - conventional DC 2 subpopulation activates moDCs to promote cyclic di-GMP mucosal adjuvant responses in vivo. Mucosal Immunol. 12(1):277-289 16. Steven M Blaauboer wt al. 2015. The mucosal adjuvant cyclic di-GMP enhances antigen uptake and selectively activates pinocytosis-efficient cells in vivo. Elife. 4:e06670 17. Scott M Mueller et al. 2016. Tissue-resident memory T cells: local specialists in immune defence. Nat Rev Immnol. 16(2):79-89 18. Derk Amsen et al. 2018. Tissue-resident memory T cells at the center of immunity to solid tumors. Nat Immunol. 19(6):538-546 19. Salvador Iborra et al. 2016. Optimal Generation of Tissue-Resident but Not Circulating Memory T Cells during Viral Infection Requires Crosspriming by DNGR-1+ Dendritic Cells. Immunity. 45(4):847-860 20. Sandra Bajaña et al. 2020. IRF4 and IRF8 Act in CD11c+ Cells To Regulate Terminal Differentiation of Lung Tissue Dendritic Cells. 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Mucosal Immunology. 11(6):1763-1776. 32. Hayley A. Croom et al. 2011. Memory precursor phenotype of CD8+ T cells reflects early antigenic experience rather than memory numbers in a model of localized acute influenza infection. Eur J Immuno. 41(3):682-93 33. Bernardo S Reis et al. 2014. Transcription factor T-bet regulates intraepithelial lymphocyte functional maturation. Immunity. 41(2):244-56 34. Laura K. Mackay et al. 2015. T-box Transcription Factors Combine with the Cytokines TGF-b and IL-15 to Control Tissue-Resident Memory T Cell Fate. Immunity. 43(6):1101-11 35. J Justin Milner et al. 2017. Runx3 programs CD8 + T cell residency in non-lymphoid tissues and tumours. Nature. 552(7684):253-257 36. Dapeng Wang et al. 2018. The Transcription Factor Runx3 Establishes Chromatin Accessibility of cis-Regulatory Landscapes that Drive Memory Cytotoxic T Lymphocyte Formation. Immunity. 48(4):659-674 37. A L Silvia et al. 2016. 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Transient enhanced IL-2R signaling early during priming rapidly amplifies development of functional CD8+ T effector-memory cells. J Immunol. 189(9):4321-30 | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/59206 | - |
dc.description.abstract | 樹突細胞對於活化抗流感病毒的T細胞免疫反應相當的重要,但是目前對於樹突細胞是如何調節形成肺部記憶型T細胞仍不是非常的清楚。目前發現的肺部樹突細胞主要有三群:CD103+的樹突細胞、CD11b+的樹突細胞以及單核球衍伸的樹突細胞。根據先前許多研究發現這三種樹突細胞對於建立肺部記憶型T細胞皆非常重要,但是哪一群樹突細胞對於建立肺部駐留記憶型T細胞扮演最主要的角色抑或是不同時間不同樹突細胞所扮演的角色目前仍不是非常清楚。本篇研究中發現,CpG最主要傾向刺激CD11b+樹突細胞,此外我也發現以PLGA包裹CpG以及OVA-I相較於其他疫苗佐劑的組別可以產生最多數量的肺部常駐型記憶T細胞。另外,我也更深入探討了之前比較少討論的肺部常駐型記憶T細胞的前體發現肺部T細胞中Runx3的表達量會隨著時間的推移而發生改變且與肺部常駐型記憶T細胞的前體的數目有一定的關係。最後,我發現以PLGA包裹CpG以及OVA-I所產生的肺部常駐型記憶T細胞的前體的數目有比其他組別還要多的趨勢,因此很可能是因為CpG所誘導產生的肺部常駐型記憶T細胞的前體數目就較多導致其最後所建立的肺部常駐型記憶T細胞也就較多。 | zh_TW |
dc.description.abstract | Dendritic cells play vital roles in establishing the T cell immunity against influenza virus infection. However, it is still unclear about how pulmonary dendritic cells ( DCs ) modulate the establishment of lung resident-memory T cells ( TRM cells ). There are three main subsets of DCs in lung: CD103+ DCs, CD11b+ resident DCs and monocyte-derived DCs. Many previous studies used the depletion systems to prove that each lung dendritic cell subset is important in establishing TRM cells; nevertheless, which subset of DCs play a dominant role in the formulation of DCs is still unknown. In this study, we found that each individual adjuvant can stimulate different subsets of DCs, and among them CpG seems to primarily stimulate CD11b+ DCs. In addition, we found that use of PLGA nanoparticles encapsulating CpG and antigenic class I MHC-restricted peptide could induce much more TRM cells than the other adjuvants. Besides, we analyze the TRM precursors, and found that the expression level of Runx3 is related to the numbers of TRM precursors. Furthermore, nanoparticles encapsulating CpG and antigenic class I MHC-restricted peptide can induce more TRM precursors. In summary, CpG can induce more TRM precursors and this might be the reason that CpG can induce more TRM cells. | en |
dc.description.provenance | Made available in DSpace on 2021-06-16T09:17:50Z (GMT). No. of bitstreams: 1 U0001-1408202015002100.pdf: 13634061 bytes, checksum: c30eea929f49991b68d5b93048f79881 (MD5) Previous issue date: 2020 | en |
dc.description.tableofcontents | 致謝………..………………………………………………………………………… 3 摘要………..………………………………………………………………………... 7 Abstract……………………………..……………………………………………...8 1. Introduction….…………………………………………………………………10 1-1 Influenza virus…………………………………………………………….10 1-2 Current influenza vaccine…………………………………………….. 11 1-3 Lung dendritic cells and their function in antiviral immunity….. 12 1-3-1 Dendritic cells and adjuvants……………………………………… 13 1-4 Memory T cells………………………………………………………….. 15 1-4-1 Dendritic cells and tissue-resident memory T cells…………… 16 1-4-2 The role of tissue-resident memory T cells in antiviral responses and their shortcomings………………………………. 17 1-4-3 Recent strategy to make optimal TRM cells ………………………. 18 1-4-4 Tissue-resident memory T cell precursors……………………… 20 1-5 Nanoparticle Vaccine………………………………………………... 21 2. Specific aim…………………………………………………………………... 23 3. Materials and Methods……………………………………………………... 24 3-1 Mice………………………………………………………………………...24 3-2 Splenocytes sorting and adoptive transfer…………………………24 3-3 PLGA nanoparticles preparation……………………………………...25 3-4 Intranasal immunization of mice………………………………………25 3-5 In vivo staining………………………………………………………….. 26 3-6 Lymphocytes isolation………………………………………………….26 3-7 Lung and mediastinal lymph node dendritic cells isolation………27 3-8 Analyze of OVA257-264 and OVA323-339 specific T cells……………….28 3-9 Cell staining, antibodies and flow cytometry……………………….28 3-10 Statistical analysis……………………………………………………..29 4. Results…………………………………………………………………………31 4-1 Different adjuvants stimulate different subsets of lung dendritic cells ………………………………………………………………………..31 4-2 Each adjuvant induces different activated level of CD4+ T cells or CD8+ T cells effector responses……………………………………….32 4-3 Titration of PLGA nanoparticles for induction of optimal CD8+ effector T cells responses ………………………...............................33 4-4 PLGA nanoparticles encapsulating different adjuvants induce similar CD8+ effector T cells responses……………………………35 4-5 CpG adjuvanted PLGA nanoparticles induces much more tissue-resident memory T cells in lung………………………………………35 4-6 Analysis of the TRM precursors ………………………………………36 4-7 TRM precursors induced by PLGA encapsulated with different adjuvants and OVA-I……………………………………………………..38 5. Discussion……………………………………………………………………..39 5-1 Conclude our findings…………………………………………………..39 5-2 The limitation of using free-form adjuvants to analyze the activation of different subsets of lung dendritic cells……………..39 5-3 The advantage of using PLGA nanoparticles to analyze the differences of dendritic cells activation and T cell responses induced by different adjuvants……………………………………….40 5-4 The reason why PLGA ( CpG + OVA-I ) can induce more TRM cell in lung ……………………………………………………………….………..41 5-5 The expression level of CD127 in TRM cells and TRM precursors ……………………………………………………….………..41 5-6 The expression level of Runx3 correlate with the TRM cell numbers……………………………………………………………………...42 5-7 R848 is not able to be encapsulated into PLGA nanoparticles…...42 5-8 The future outlook of CpG-adjuvanted PLGA nanoparticles for vaccine development……………………………………………………...43 Figures Figure1. The activation of different subsets of lung dendritic cells by different adjuvants. …………………………………………………..44 Figure 2. The effects of different adjuvants to CD4+ and CD8+ effector T cells………………………………………………………………………47 Figure 3. CD8+ effector responses induced by different doses of PLGA ( CpG + OVA-I ) …………………………………………………………51 Figure 4. CD8+ effector T cells responses induced by PLGA encapsulated with different adjuvants and OVA-I ………………………………..54 Figure 5. TEM, TCM and TRM cell numbers induced by PLGA encapsulated with different adjuvants and OVA-I…………………………………57 Figure 6. Memory T cell precursors and expression level of CD127 and Runx3 at different time points………………………………………61 Figure 7. Memory T cell precursors induced by PLGA encapsulated with different adjuvants and OVA-I………………………………………66 Supplementary 1. Antiviral cytokines released by different subsets of lung DCs………………………………………………………………….69 Supplementary 2. The variation of body weight induced by different adjuvanted PLGA nanoparticles……………………………………70 References………………………………………………………………………...71 | |
dc.language.iso | en | |
dc.title | 利用不同疫苗佐劑探討不同肺部樹突細胞對於建立抗流感病毒的T細胞免疫反應所扮演的角色 | zh_TW |
dc.title | To study the effects of adjuvants on dendritic cells in establishing T cell immunity against influenza virus | en |
dc.type | Thesis | |
dc.date.schoolyear | 108-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 胡哲銘(Che-Ming Hu),顧家綺(Chia-Chi Ku) | |
dc.subject.keyword | 流感疫苗,T細胞免疫, | zh_TW |
dc.subject.keyword | Influenza vaccine,T cell immunity, | en |
dc.relation.page | 75 | |
dc.identifier.doi | 10.6342/NTU202003420 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2020-08-17 | |
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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