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| ???org.dspace.app.webui.jsptag.ItemTag.dcfield??? | Value | Language |
|---|---|---|
| dc.contributor.advisor | 賈景山 | zh_TW |
| dc.contributor.advisor | Jean-San Chia | en |
| dc.contributor.author | 張仕宸 | zh_TW |
| dc.contributor.author | Shih-Chen Chang | en |
| dc.date.accessioned | 2023-05-18T17:04:13Z | - |
| dc.date.available | 2025-12-12 | - |
| dc.date.copyright | 2023-06-07 | - |
| dc.date.issued | 2022 | - |
| dc.date.submitted | 2023-01-15 | - |
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Cellular Senescence: Aging, Cancer, and Injury. Physiol Rev 99, 1047-1078, doi:10.1152/physrev.00020.2018 (2019). 48 Goronzy, J. J. & Weyand, C. M. Mechanisms underlying T cell ageing. Nat Rev Immunol, doi:10.1038/s41577-019-0180-1 (2019). 49 Chiu, Y. L. et al. Emergence of T cell immunosenescence in diabetic chronic kidney disease. Immun Ageing 17, 31, doi:10.1186/s12979-020-00200-1 (2020). 50 Ding, Z. C. et al. IL-7 signaling imparts polyfunctionality and stemness potential to CD4(+) T cells. Oncoimmunology 5, e1171445, doi:10.1080/2162402X.2016.1171445 (2016). 51 Chiu, Y. L. et al. Sprouty-2 regulates HIV-specific T cell polyfunctionality. J Clin Invest 124, 198-208 52 Vudattu, N. K., Magalhaes, I., Schmidt, M., Seyfert-Margolis, V. & Maeurer, M. J. Reduced numbers of IL-7 receptor (CD127) expressing immune cells and IL-7-signaling defects in peripheral blood from patients with breast cancer. Int J Cancer 121, 1512-1519, doi:10.1002/ijc.22854 (2007). 53 Gao, J., Zhao, L., Wan, Y. Y. & Zhu, B. Mechanism of Action of IL-7 and Its Potential Applications and Limitations in Cancer Immunotherapy. Int J Mol Sci 16, 10267-10280, doi:10.3390/ijms160510267 (2015). 54 Miller, P. W. et al. Intratumoral administration of adenoviral interleukin 7 gene-modified dendritic cells augments specific antitumor immunity and achieves tumor eradication. Hum Gene Ther 11, 53-65, doi:10.1089/10430340050016157 (2000). | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/87324 | - |
| dc.description.abstract | CD127 (IL-7R)介白素七號α鏈受體蛋白之表現與CD8記憶型Ｔ細胞表現型與功能有顯著的關係。在先前研究中顯示口腔癌病人的周邊血與腫瘤環境中，CD127 (IL-7R)介白素七號α鏈受體蛋白在CD8記憶型Ｔ細胞表現高低，亦可代表記憶型細胞功能性差異。在目前研究中並無人類介白素七號α鏈受體蛋白差異性表現CD8記憶型Ｔ細胞次群與T細胞受體庫之間的關聯之研究。此外，維持介白素七號α鏈受體蛋白差異性表現CD8記憶型Ｔ細胞次群所需的基因表現亦未全然知曉。在本研究中，我們分析CD127 (IL-7R)介白素七號α鏈受體蛋白之表現高低之記憶型細胞其T細胞受體庫特性與基因微陣列分析表現之差異。
我們透過T細胞受體庫分析發現CD127 (IL-7R)介白素七號α鏈受體蛋白高表現之T細胞相較於低表現者，具有較高的T細胞受體庫多樣性。而如此現象並不受傳統CD8記憶型Ｔ細胞表現型之CD45RO+ TEM 或 CD45RA+TEMRA之細胞型所限制。介白素七號α鏈受體蛋白高表現之T細胞受體庫多樣性高同時代表著較低的株落增值現象。在基因微陣列分析中，介白素七號α鏈受體蛋白低表現之T細胞相較於高表現者表現更多的活化態功能性基因，包含顆粒酶B、穿孔酶、顆粒酶H與泛抑制性殺傷免疫球蛋白樣受體。此外，介白素七號α鏈受體蛋白低表現之T細胞相較於高表現者其經T細胞受器激活和細胞因子驅動的增殖相比，表現出較低的表現型可塑性。在受體庫分析上，介白素七號α鏈受體蛋白高表現之T細胞和介白素七號α鏈受體蛋白低表現之T細胞之間的T細胞受體庫共享顯著高於TEM 和 TEMRA群體之間，並且介白素七號α鏈受體蛋白低表現之T細胞可以在體外穩態細胞因子刺激下從介白素七號α鏈受體蛋白高表現之T細胞細胞誘導。在腫瘤浸潤CD8 T細胞受體庫中也保留了類似的介白素七號α鏈受體蛋白低表現之T細胞明顯株落增殖。這些功能性基因表現的結果是與小鼠相似的。人類記憶CD8 T 細胞的功能可以僅基於介白素七號α鏈受體蛋白進行唯一有效區分。並且無論在週邊血或局部腫瘤微環境中，介白素七號α鏈受體蛋白高表現亞群和低表現亞群之間的維持平衡是無論在TEM 或 TEMRA CD8 記憶T細胞分群都適用的。 | zh_TW |
| dc.description.abstract | We reported and hypothesized that CD127 (IL-7R) expression as either high or low could identify human CD8+ T memory cell subsets with distinct functionalities regardless of their CD45RO+ TEM or CD45RA+TEMRA phenotypes. Here, we further analyzed CD127hi or CD127lo TEM and TEMRA cells for their Vβ-CDR3 repertoire and gene expression profiles to validate our hypothesis. The CD127hi subsets exhibited higher TCR diversity coupled with lower frequency of clonal expansion compared to CD127lo populations within either TEM or TEMRA. Both TEM and TEMRA CD127lo populations showed higher gene expression associated with activated functionality, including perforin, granzyme B, granzyme H, and pan-inhibitory killer immunoglobulin-like receptors, exhibited lower phenotype plasticity upon TCR activation and cytokine-driven proliferation, when compared to their CD127hi counterparts. TCR repertoire sharing is significantly higher between CD127hi and CD127lo than between TEM and TEMRA populations, and CD127lo cells can be induced from CD127hi cells upon in vitro homeostatic cytokines stimulation, suggesting differentiation from CD127hi into CD127lo CD8+ T cell. Similar repertoire sharing with pronounced clonal expansion is also preserved in the tumor infiltrated CD8+ T cell. These results suggested that the functionality of human memory CD8+ T cell, similar to mouse, can be uniquely distinguished based on CD127 alone, and homeostasis mediated through IL-7R between CD127 high and low subsets is maintained within either TEM or TEMRA CD8+ memory T cell peripheral or local microenvironment. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2023-05-18T17:04:13Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2023-05-18T17:04:13Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 誌謝 I
中文摘要 II Abstract IV 目錄 .V 圖目錄 VII Chapter 1. Introduction 1 1.1. Surface expression of human peripheral blood CD8+ T cells 1 1.2. Tissue-resident or regional memory CD8+ T cells 1 1.3. Expression of IL-7R (CD127) in human T cell differentiation 2 Chapter 2. Purposes and Aims 4 Chapter 3. Materials and Methods 5 3.1. Human Subjects 5 3.2. Peripheral or tumor-infiltrating CD8+ T cells isolation and proliferation assay 5 3.3. T cell receptor CDR3 sequencing and repertoire similarity or diversity analyses 7 3.4. Microarray analysis 8 3.5. Gene set enrichment analysis (GSEA) 9 3.6. Pathway enrichment analysis 9 3.7. Statistical analysis 10 Chapter 4. Result 11 4.1. CD127hi memory CD8+ T subsets are of higher TCR repertoire diversity compared with CD127lo T cells 11 4.2. CD127hi memory CD8+ T subsets sharing TCR repertoire with CD127lo in either TEM or TEMRA 12 4.3. Transcriptomic analyses reveal distinct functional specializations of CD127-defined memory CD8+ T cell subsets 16 4.4. CD127lo cells are more differentiated than CD127hi cells in both TEM and TEMRA subsets 21 4.5. Discriminated proliferation potentials of CD127hi and CD127lo T cell subsets in response to cytokines 21 4.6. TCR repertoire sharing between TIL and PBMC 23 Chapter 5. Discussion 25 Chapter 6. Reference 31 Chapter 7. Figures 36 Chapter 8. Supplementary data 48 | - |
| dc.language.iso | en | - |
| dc.subject | CD8記憶型T細胞 | zh_TW |
| dc.subject | 介白素七號受體 | zh_TW |
| dc.subject | Ｔ細胞受體庫 | zh_TW |
| dc.subject | IL-7 receptor | en |
| dc.subject | CD8 memory T cell | en |
| dc.subject | TCR repertoire | en |
| dc.title | 人類CD8+CD127hi及CD127lo的TEM與TEMRA次群 T細胞受體庫分析與特異性基因表現 | zh_TW |
| dc.title | CD127-expression identifies human CD8+ TEM and TEMRA revealed by TCR repertoire and gene expression | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 111-1 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 顧家綺;俞松良 | zh_TW |
| dc.contributor.oralexamcommittee | Chia-Chi Ku;Sung-Liang Yu | en |
| dc.subject.keyword | 介白素七號受體,CD8記憶型T細胞,Ｔ細胞受體庫, | zh_TW |
| dc.subject.keyword | IL-7 receptor,CD8 memory T cell,TCR repertoire, | en |
| dc.relation.page | 52 | - |
| dc.identifier.doi | 10.6342/NTU202300042 | - |
| dc.rights.note | 同意授權(限校園內公開) | - |
| dc.date.accepted | 2023-01-16 | - |
| dc.contributor.author-college | 醫學院 | - |
| dc.contributor.author-dept | 免疫學研究所 | - |
| dc.date.embargo-lift | 2027-12-12 | - |
| Appears in Collections: | 免疫學研究所 | |
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