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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 顧家綺 | |
| dc.contributor.author | Ping-Fang Chang | en |
| dc.contributor.author | 張萍芳 | zh_TW |
| dc.date.accessioned | 2021-06-15T02:24:05Z | - |
| dc.date.available | 2014-09-15 | |
| dc.date.copyright | 2009-09-15 | |
| dc.date.issued | 2009 | |
| dc.date.submitted | 2009-08-18 | |
| dc.identifier.citation | Ahmad, A., Sharif-Askari, E., Fawaz, L., and Menezes, J. (2000). Innate immune response of the human host to exposure with herpes simplex virus type 1: in vitro control of the virus infection by enhanced natural killer activity via interleukin-15 induction. J Virol 74, 7196-7203.
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A regulatory role of interleukin 15 in wound healing and mucosal infection in mice. J Leukoc Biol 83, 165-172. Kennedy, M.K., Glaccum, M., Brown, S.N., Butz, E.A., Viney, J.L., Embers, M., Matsuki, N., Charrier, K., Sedger, L., Willis, C.R., et al. (2000). Reversible defects in natural killer and memory CD8 T cell lineages in interleukin 15-deficient mice. J Exp Med 191, 771-780. Kishimoto, T., Taga, T., and Akira, S. (1994). Cytokine signal transduction. Cell 76, 253-262. Kodukula, P., Liu, T., Rooijen, N.V., Jager, M.J., and Hendricks, R.L. (1999). Macrophage control of herpes simplex virus type 1 replication in the peripheral nervous system. J Immunol 162, 2895-2905. Lodolce, J., Burkett, P., Koka, R., Boone, D., Chien, M., Chan, F., Madonia, M., Chai, S., and Ma, A. (2002). Interleukin-15 and the regulation of lymphoid homeostasis. Mol Immunol 39, 537-544. Loser, K., Mehling, A., Apelt, J., Stander, S., Andres, P.G., Reinecker, H.C., Eing, B.R., Skryabin, B.V., Varga, G., Schwarz, T., et al. (2004). Enhanced contact hypersensitivity and antiviral immune responses in vivo by keratinocyte-targeted overexpression of IL-15. Eur J Immunol 34, 2022-2031. Malek, T.R., Yu, A., Vincek, V., Scibelli, P., and Kong, L. (2002). CD4 regulatory T cells prevent lethal autoimmunity in IL-2Rbeta-deficient mice. Implications for the nonredundant function of IL-2. Immunity 17, 167-178. Mattei, F., Schiavoni, G., Belardelli, F., and Tough, D.F. (2001). IL-15 is expressed by dendritic cells in response to type I IFN, double-stranded RNA, or lipopolysaccharide and promotes dendritic cell activation. J Immunol 167, 1179-1187. McInnes, I.B., and Gracie, J.A. (2004). Interleukin-15: a new cytokine target for the treatment of inflammatory diseases. Curr Opin Pharmacol 4, 392-397. Mintern, J.D., Guillonneau, C., Carbone, F.R., Doherty, P.C., and Turner, S.J. (2007). Cutting edge: Tissue-resident memory CTL down-regulate cytolytic molecule expression following virus clearance. J Immunol 179, 7220-7224. Mohamadzadeh, M., Berard, F., Essert, G., Chalouni, C., Pulendran, B., Davoust, J., Bridges, G., Palucka, A.K., and Banchereau, J. (2001). Interleukin 15 skews monocyte differentiation into dendritic cells with features of Langerhans cells. J Exp Med 194, 1013-1020. Nandakumar, S., Woolard, S.N., Yuan, D., Rouse, B.T., and Kumaraguru, U. (2008). Natural killer cells as novel helpers in anti-herpes simplex virus immune response. J Virol 82, 10820-10831. Olsen, S.K., Ota, N., Kishishita, S., Kukimoto-Niino, M., Murayama, K., Uchiyama, H., Toyama, M., Terada, T., Shirouzu, M., Kanagawa, O., et al. (2007). Crystal Structure of the interleukin-15.interleukin-15 receptor alpha complex: insights into trans and cis presentation. J Biol Chem 282, 37191-37204. Peschon, J.J., Morrissey, P.J., Grabstein, K.H., Ramsdell, F.J., Maraskovsky, E., Gliniak, B.C., Park, L.S., Ziegler, S.F., Williams, D.E., Ware, C.B., et al. (1994). Early lymphocyte expansion is severely impaired in interleukin 7 receptor-deficient mice. J Exp Med 180, 1955-1960. Popp, R.A., Bailiff, E.G., Skow, L.C., Johnson, F.M., and Lewis, S.E. (1983). Analysis of a mouse alpha-globin gene mutation induced by ethylnitrosourea. Genetics 105, 157-167. Reske, A., Pollara, G., Krummenacher, C., Chain, B.M., and Katz, D.R. (2007). Understanding HSV-1 entry glycoproteins. Rev Med Virol 17, 205-215. Ruckert, R., Asadullah, K., Seifert, M., Budagian, V.M., Arnold, R., Trombotto, C., Paus, R., and Bulfone-Paus, S. (2000). Inhibition of keratinocyte apoptosis by IL-15: a new parameter in the pathogenesis of psoriasis? J Immunol 165, 2240-2250. Sprecher, E., and Becker, Y. (1986). Skin Langerhans cells play an essential role in the defense against HSV-1 infection. Arch Virol 91, 341-349. 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J Biol Chem 271, 23055-23060. van Lint, A., Ayers, M., Brooks, A.G., Coles, R.M., Heath, W.R., and Carbone, F.R. (2004). Herpes simplex virus-specific CD8+ T cells can clear established lytic infections from skin and nerves and can partially limit the early spread of virus after cutaneous inoculation. J Immunol 172, 392-397. Wakim, L.M., Jones, C.M., Gebhardt, T., Preston, C.M., and Carbone, F.R. (2008). CD8(+) T-cell attenuation of cutaneous herpes simplex virus infection reduces the average viral copy number of the ensuing latent infection. Immunol Cell Biol 86, 666-675. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/43597 | - |
| dc.description.abstract | 介白質-15（interleukin-15，IL-15）是細胞激素的一種。除了參與免疫反應之外，同時也對體內其他生理機能扮演重要的角色，像是骨骼肌的代謝及角質細胞的增生。由於IL-15的作用廣泛，因此其表達在轉錄、轉譯及胞內運送的階段都被嚴密地調控。同時IL-15被發現有多種選擇性剪接異構體存在，除了對IL-15的分泌影響外，目前對於IL-15選擇性剪接異構體對於IL-15本身的調控及影響仍不清楚。在我們的研究中，利用國家型基因突變鼠核心實驗室以ENU誘導突變所建立的突變鼠品系191(p191)，經過人類疱疹一型病毒（Human Herpes Simplex Virus-1，HSV-1）的感染模式，希望能進一步了解IL-15選擇性剪接異構體對於CD8+ T細胞的免疫反應的影響。
我們透過表皮感染B6及p191小鼠HSV-1後發現，雖然B6小鼠在病毒感染後第4到5天形成傷口，並在第十天左右癒合；然而p191小鼠的疱疹傷口不但在病毒感染後第2到3天就開始出現，而且傷口可以持續到第12天左右才癒合。利用病毒溶斑的檢測方法我們也發現p191小鼠皮膚可以偵測到比B6小鼠中有更高的病毒數量(在感染後第七天有1000倍的差異)。結果顯示HSV-1在p191的皮膚不但可以複製地多，同時造成較大的皮膚傷口與修復的延遲。雖然在未感染的情況下，p191小鼠中NK1.1+細胞的數目就低於B6小鼠(50%左右)，但是經過HSV-1感染後，p191小鼠的NK1.1+細胞增加的倍數和B6小鼠相近(10倍左右)。p191小鼠中較少量的NK1.1+細胞可能直接或間接影響到皮膚中病毒的清除。不論是B6或是p191小鼠感染HSV-1後，引流淋巴結內的CD8+ T細胞總數均明顯增加(最高3.5倍的增加)。利用MHC Class I的tetramer進一步地分析比較兩組小鼠經過HSV-1感染後具有gB抗原特異性的CD8+ T細胞群的生成情形，我們發現這些具有抗原特異性的CD8+ T細胞在感染初期數目上差異不大，但是兩組小鼠的引流淋巴結與脾臟分佈則有明顯不同(B6小鼠中主要聚集在引流淋巴結，p191小鼠則是脾臟)。P191小鼠的抗原特異性CD8+ T細胞也可能因為Bcl-2蛋白表達下降而影響該組細胞的長期存活性。同時，我們也發現了皮膚衍生的樹突細胞感染HSV-1後移動到引流淋巴結的時間在B6(高峰於感染後第三天)與p191(高峰於感染後第五天)也不相同。究竟樹突細胞的抗原呈現功能與刺激活化CD8+ T細胞的能力是否在p191小鼠中有被改變，以及這些機制是否能夠直接地或是間接地影響皮膚傷口的嚴重程度、病毒繁殖複製與病毒清除的能力等方面，仍有待進一步地探討。 | zh_TW |
| dc.description.provenance | Made available in DSpace on 2021-06-15T02:24:05Z (GMT). No. of bitstreams: 1 ntu-98-R96449007-1.pdf: 8318406 bytes, checksum: a6d755928de06e7325bba16817ca2302 (MD5) Previous issue date: 2009 | en |
| dc.description.tableofcontents | 中文摘要------------------------------------------------------------1
英文摘要------------------------------------------------------------3 第一章 緒論---------------------------------------------------------4 第一節 細胞激素與免疫反應---------------------------------------4 1. 調控細胞激素表達的機制-----------------------------------5 2. IL-2 cytokine family異構體的生物特性-------------------------5 IL-2 cytokine family------------------------------------5 IL-2 cytokine family與選擇性剪接異構體------------------6 3. 細胞激素異構體的應用發展性-------------------------------7 第二節 T細胞的生存---------------------------------------------8 1. naïve T細胞的生存-----------------------------------------8 2. 活化的T細胞的生存---------------------------------------8 抗原專一性的T細胞偵測-------------------------------9 3. 記憶T(memory T cell)細胞的生存-----------------------------9 第三節 動物模式在生物學研究上的重要性---------------------------9 1. ENU的致突變機制----------------------------------------10 2. 從表型篩選到基因檢測------------------------------------10 3. ENU突變鼠在免疫學研究上的應用--------------------------11 Pedigree 191 (P191) -----------------------------------12 IL-15的生理意義-------------------------------------12 4. P191 基因突變鼠免疫偏差(Immune Deviation)之探討-----------13 第四節 人類單純性疱疹一型病毒的感染與免疫反應------------------14 1. HSV-1的特徵---------------------------------------------14 2. 宿主的防禦機制------------------------------------------14 HSV-1引發的先天性免疫反應--------------------------15 HSV-1引發的後天性免疫反應--------------------------15 第二章 材料與方法--------------------------------------------------17 第三章 實驗結果----------------------------------------------------37 1. p191小鼠的特徵------------------------------------------37 2. HSV-1感染小鼠形成疱疹傷口之現象-------------------------37 3. HSV-1在B6及p191皮膚中的複製----------------------------38 4. NK細胞的增加--------------------------------------------39 5. CD8+ T細胞的活化----------------------------------------40 6. 引流淋巴結中DC的增生與活化-----------------------------45 第四章 討論--------------------------------------------------------49 1. 皮膚中的具感染力的病毒效價在B6及p191小鼠間的差異-------49 2. NK1.1+細胞在抗HSV-1感染的角色--------------------------51 3. CD8+ T細胞在抗HSV-1病毒感染中扮演的角色----------------52 4. 樹突細胞對活化及維持CD8+ T細胞的重要性-----------------53 5. 總結----------------------------------------------------55 第五章 參考資料----------------------------------------------------57 第六章 圖表--------------------------------------------------------63 圖表目次 1. 小鼠周邊血中NK1.1+細胞及CD44hi CD8+ T細胞表達程度之比較--------63 2. HSV-1小鼠上皮組織之操作-----------------------------------------64 3. HSV-1感染小鼠後皮膚傷口的比較-----------------------------------65 4. HSV-1感染小鼠上皮組織之皮膚病毒效價偵測-------------------------67 5. 小鼠引流淋巴結及脾臟中NK1.1+細胞數量之變化---------------------68 6. 小鼠引流淋巴結及脾臟中CD8+ T細胞數量之變化---------------------69 7. 小鼠引流淋巴結及脾臟中CD44hi CD8+ T細胞數量之變化--------------70 8. HSV-1感染小鼠上皮組織具抗原專一性CD8+ T細胞之偵測-------------71 9. 小鼠引流淋巴結及脾臟中具抗原專一性CD8+ T細胞數量之變化---------72 10. 小鼠脾臟中抗原特異性CD8+ T細胞Bcl-2表達量之變化---------------73 11. HSV-1感染小鼠上皮組織引流淋巴結中皮膚衍生樹突細胞之偵測--------74 12. 小鼠引流淋巴結中樹突細胞之細胞結構-----------------------------75 | |
| dc.language.iso | zh-TW | |
| dc.subject | DC | zh_TW |
| dc.subject | IL-15 | zh_TW |
| dc.subject | HSV-1 | zh_TW |
| dc.subject | skin | zh_TW |
| dc.subject | NK | zh_TW |
| dc.subject | CD8 | zh_TW |
| dc.title | 以ENU基因突變鼠動物模式探討介白質-15異構體對單純性疱疹一型病毒引起CD8+ T細胞的免疫反應之影響 | zh_TW |
| dc.title | Infection of ENU mutant mice with Human Herpes Simplex Virus-1 (HSV-1) to investigate the effects of IL-15 splice variant on CD8+ T cell-mediated immunity | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 97-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 伍安怡,孔祥智 | |
| dc.subject.keyword | IL-15,HSV-1,skin,NK,CD8,DC, | zh_TW |
| dc.relation.page | 75 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2009-08-18 | |
| 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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