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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 孔祥智(Hsiang-Chih Kung) | |
dc.contributor.author | Jen-Ju Lin | en |
dc.contributor.author | 林珍如 | zh_TW |
dc.date.accessioned | 2021-05-17T09:17:07Z | - |
dc.date.available | 2012-12-31 | |
dc.date.available | 2021-05-17T09:17:07Z | - |
dc.date.copyright | 2012-09-18 | |
dc.date.issued | 2012 | |
dc.date.submitted | 2012-07-26 | |
dc.identifier.citation | Au-Yeung, B.B., Deindl, S., Hsu, L.Y., Palacios, E.H., Levin, S.E., Kuriyan, J., and Weiss, A. (2009). The structure, regulation, and function of ZAP-70. Immunol Rev 228, 41-57.
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/6734 | - |
dc.description.abstract | P358小鼠為ENU的誘導產生的突變小鼠,其ZAP70蛋白激酶中發生了單一的氨基酸置換,第563號半胱胺酸(cysteine)被置換成絲氨酸(serine)。此小鼠於週齡五週大即產生自體免疫抗體,故給予小鼠名稱“Sap”意指“血清抗體陽性”。此研究利用免疫螢光染色法檢測血清中的抗體和沉積在腎臟腎小球的免疫球蛋白以及西方墨點法來分析隨著時間的推移,自體抗體特性的變化。Sap小鼠有著接近系統性紅斑狼瘡疾病的症狀,具有大量的自體抗體在血清內和免疫複合物沉積在腎絲球中。Sap小鼠在週齡五週大時主要產生抗胞質抗體, 週齡八週以上主要產生抗核抗體,隨著年齡變化,Sap小鼠增加自體抗體總量和認識的抗原種類。抗核抗體主要屬於IgG2a亞類,而形成的免疫複合物多數為IgM。在CD4+ T細胞及γ-干擾素缺失的Sap小鼠中,IgG2a抗核抗體的消失和免疫複合物沉積量降低,證明了CD4+ T細胞及γ-干擾素在Sap小鼠的自身免疫反應的重要性。將Sap小鼠的CD4 T+ 細胞過繼轉移(adoptive transfer)至Sap-CD4-KO小鼠體內可成功誘導抗核抗體的產生但是若過繼轉移至Sap-IFN-γ-KO小鼠體內則無法產生抗核抗體,然而仍然可見抗胞質抗體。此研究證明了CD4+ T細胞和γ-干擾素在誘發抗核抗體反應中扮演重要角色,並提供了除了CD4+ T細胞以外由其他細胞提供γ-干擾素主要來源的可能性。 | zh_TW |
dc.description.abstract | An ENU-induced mutant mouse with a point mutation in the Zap70 gene was studied. This mutant Zap70 gene encodes a Zap70 protein with a single C to S amino acid substitution at residue 563. This Zap70 mutant mouse spontaneously produced autoantibody and was named “Sap” for “serum autoantibody positive.” The autoantibody response in Sap mice, as a function of age, was characterized by immunofluorescence, Western blotting, and immune complex deposition techniques. Sap mice at 5 wks of age made primarily anti-cytoplasmic autoantibodies. Sap mice over 8 wks of age, on the other hand, made predominantly anti-nuclear autoantibodies (ANA), most of which were of the IgG2a isotype. Sap mice also displayed glomeruli-associated immune complex deposition, most of which were of the IgM isotype. IgG2a ANA and immune complex deposition responses were lost in Sap-CD4-KO and Sap-IFN-γ-KO mice. Adoptive transfer of Sap CD4+ T cells restored the deficient ANA response in Sap-CD4-KO but not Sap-IFN-γ-KO hosts. Despite the loss of ANA, anti-cytoplasmic autoantibody response was still observed in Sap-IFN-γ-KO mice. These results clearly show the key roles played by CD4+ T cells and IFN-γ in the induction of the ANA response. They also implicate the importance of cells other than CD4+ T cells as the provider of IFN-γ in the induction of the ANA response. | en |
dc.description.provenance | Made available in DSpace on 2021-05-17T09:17:07Z (GMT). No. of bitstreams: 1 ntu-101-R99449006-1.pdf: 2760998 bytes, checksum: ccc5a86be26c8142f384a05805c75f51 (MD5) Previous issue date: 2012 | en |
dc.description.tableofcontents | Acknowledgements i
Abstract ii 中文摘要 iii Introduction 1 Materials and Methods 9 2.1 Mice 9 2.2 Cell lines 9 2.3 Autoantibody Immunofluorescence staining 10 2.4 Autoantibody detection using frozen tissues 12 2.5 Mitochondria staining 13 2.6 Western blot 14 2.7 Immunofluorescence staining of frozen tissues 16 2.8 Histological analysis 17 2.9 Anti-CD4 Treatments 18 2.10 Surface marker expression analysis by flow cytometer (FACS) 19 2.11 Spleen CD4+ T cell isolation by panning 20 2.12 Electronic cell sorting 21 2.13 Adoptive Transfer 22 2.14 Tracing of Donor cell persistence by flow cytometry 22 Results 24 3.1 Sap mice produce autoantibody 24 3.2 Assorted autoantibody reactivity in Sap sera as a function of age 26 3.3 Glomerular deposits of Ig developed at early age in Sap mice 28 3.4 Presence of predominant IgG2a, IgG1, but not IgM anti-nuclear autoantibody 29 3.5 Renal immune complex deposits were mostly IgM type 30 3.6 CD4+ T cells are required for germinal center reaction in Sap mice 31 3.7 IFN-γ-dependency of autoantibody response in Sap mice 33 3.8 Reduced Ig deposits in the absence of IFN-γ 33 3.9 Predominance of IgG1 and IgG2b subclasses of anti-cytoplasmic autoantibodies in Sap-IFN-γ-KO mice 34 3.10 Sap CD4+ T cells can reconstitute anti-nuclear autoantibody response in Sap-CD4-KO mice but not in Sap-IFN-γ-KO 34 3.11 Autoantibody response in Sap mice is partially dependent on NKT cells but not CD8+ T cells 36 Discussion 39 4.1 Characterization of autoantibody production in Sap mice 39 4.2 Non-CD4+ T cell source of IFN-γ in autoantibody production 43 4.3 Autophagy and ANA response 46 4.4 Immune complex deposition in Sap kidney without glomerulonephritis 47 References 50 Figures 59 | |
dc.language.iso | en | |
dc.title | CD4+ T 細胞以及IFN-γ在Zap-70突變鼠之自體抗體反應所扮演的角色 | zh_TW |
dc.title | Role of CD4+ T cells and IFN-γ in autoantibody response in Zap70 mutant mice | en |
dc.type | Thesis | |
dc.date.schoolyear | 100-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 伍安怡(An-Ye Wu),李建國(Chien-Kuo Lee) | |
dc.subject.keyword | 突變小鼠,自體免疫,抗核抗體,免疫複合物,γ-干擾素, | zh_TW |
dc.subject.keyword | ENU,Zap70,autoantibody,ANA,ACA,immune complex,IgG2a,IFN-γ,germinal center, | en |
dc.relation.page | 79 | |
dc.rights.note | 同意授權(全球公開) | |
dc.date.accepted | 2012-07-27 | |
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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