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研究生:陳浩偉
研究生(外文):Chen,Hao-Wei
論文名稱:快速增生俱NKG2D的抗原專一性CD4+T細胞
論文名稱(外文):Rapid Expansion of Antigen-Specific CD4+ T Cells Expression NKG2D Receptors
指導教授:林俊銘林俊銘引用關係
指導教授(外文):Lin,Chun-Ming
學位類別:碩士
校院名稱:東吳大學
系所名稱:微生物學系
學門:生命科學學門
學類:微生物學類
論文種類:學術論文
論文出版年:2004
畢業學年度:92
語文別:中文
論文頁數:66
中文關鍵詞:被動免疫細胞療法抗原專一性T細胞
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為了增強病人自我的免疫系統,進而去抵抗腫瘤或慢性病毒性疾病,先行在體外產生免疫反應,然後將活化的抗原專一性T細胞植回病人體內是一個被相當看好的方法(被動免疫細胞療法)。一個成功的被動免疫細胞療法需要以下幾個因素:(1)分離出有功能性的抗原專一性T細胞(2)可以在體外快速地增生抗原專一性T細胞至臨床有意義的數字(3)送回病人體內的抗原專一性T細胞必須要能長時間的存活(4)建立和維持免疫反應的專一性。基於以上原因,我們研究多種細胞界素(cytokine)對於樹狀細胞所活化對B型肝炎抗原有專一性的CD4+T細胞增生的影響,包括IL-2,IL-7和IL-15。
我們研究發現利用CD3/CD28抗體、IL-7和IL-15可以在兩個星期內快速地增生對B型肝炎抗原有專一性的T細胞至臨床有意義的數字(超過1000倍),這些由IL-7和IL-15所刺激增生對B型肝炎抗原有專一性的CD4+T細胞在沒有細胞界素及有CD3抗體的刺激下,都表現出其有較高的生存能力,所以能應付植回體內後所會遇到細胞界素濃度較低及細胞自發性死亡(Activation-induced cell death)的問題。而且,這些由IL-7和IL-15所刺激增生對B型肝炎抗原有專一性的CD4+T細胞都具有4-1BB和NKG2D共刺激分子受器。
總結來說,在體外利用CD3/CD28抗體、IL-7和IL-15來刺激由樹狀細胞所活化的抗原專一性T細胞比一般只利用CD3/CD28抗體來刺激的方法更有效率。
To arm a patient’s own immune system to repel tumors and chronic viral diseases, a promising approach is to generate an immune response ex vivo, and then to transfer the fully activated antigen-specific T lymphocytes back into the patient (that is, adoptive T cell therapy). A successful adoptive T cell therapy requires following efforts: (1) isolation of functional antigen-specific T cells; (2) a rapid, multi-log expansion of antigen-specific T cells ex vivo to clinically meaningful numbers; (3) long-term survival of antigen-specific T cells after infusion; (4) establishment and maintainance of a specific immune response. In this theses, we investigated the effects of various cytokins, including interleukin(IL)-2, IL-7, and IL-15, on the expansion of dendritic cell-activated hepatitis B virus(HBV)-specific CD4 T cells.
We found that combination of CD3/CD28 antibody, IL-7, and IL-15 could rapidly expand HBV-specific CD4 T cells to clinically meaningful numbers (more than 1000 fold) in two weeks. These IL7/15-expanded HBV-specific CD4 T cells exhibited enhanced survival after cytokine withdrawal and CD3 antibody stimulation, which simulates the circumstances encountered by infused T cells and activation-induced cell death, respectively. Moreover, These IL7/15-expanded HBV-specific CD4 T cells expressed 4-1BB and NKG2D co-stimulatory receptors.
In summary, ex vivo expansion of DC-activated antigen-specific CD4 T cells with IL-7, IL-15 and anti-CD3/CD28 is more efficient than commonly used method (that is, expansion with anti-CD3/CD28).
目錄…………………………………………………………………,I.
中文摘要…………………………………………………………….II
英文摘要..………………………………………………………….IV
第一章、前言...………………………………………………………1
第二章、實驗目的…………………………………………………12
第三章、材料方法………………………………………………….13
第四章、結果……………………………………………………….31
第五章、討論………………………………………………………36
第六章、參考文獻…………………………………………………38
圖表…………………………………………………………….......45
附圖………………………………………………………………...59
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