伍安怡2018-07-092018-07-092004http://ntur.lib.ntu.edu.tw//handle/246246/25366第一部份 功能性 T 細胞對於對抗感染是非常重要的。文獻報告指出，利用其產生細胞激 素的能力所定義之功能性 T 細胞，可代表在疾病感染模式中具抗原特異性的T 細胞。在本實驗中，我們計算在脾臟中產生干擾素γ 之組織胞漿菌特異性細胞數 目，並發現一種巨噬細胞胞內病源菌-組織胞漿菌之感染可以活化 CD4 及CD8 T 細胞。CD8 T 細胞反應強度雖較CD4 T 細胞的反應強度弱，二種細胞反應之擴 張與收縮的動力學則是相同的模式。超過 90% 的產生干擾素γ 之 CD4 T 細胞 及超過 85% 的產生干擾素γ 之 CD8 T 細胞均表現高量之 CD44 。產生干擾素 γ 與高量 CD44 表現之間的高度相關性不只在反應高峰期可觀察到，在整個感染 過程均是如此。此外，廣大系列 V β 族群均會對全身性以及肺部感染產生反應， 代表在抵抗組織胞漿菌之初次免疫反應中並無使用明顯 T 細胞受體傾向。幾乎 每一個V β 族群都對產生干擾素γ 有貢獻，數個特定V β 族群組成較大比例之產 生干擾素γ 細胞。我們的研究對於後續對組織胞漿菌感染所引發之免疫反應的探 討提供基礎之了解。(此部分已被接受發表於International Immunology,November 2004) 第二部份 CD8 T 細胞對於宿主抵抗組織胞漿菌感染的貢獻，在 CD4 T 細胞完整之小鼠是 較其次的，因若去除CD8 T 細胞只會延遲但並不影響病菌的清除。然而，CD8 T 細胞在缺乏功能性CD4 T 細胞之宿主是否具有保護能力仍然需要更進一步的探討。本實驗室研究中發現，MHC class II 基因缺陷小鼠在感染組織胞漿菌後能 將病菌數量維持如同第一週之數目長達十六週，顯示CD8 T 細胞能夠限制病菌 之複製。研究結果顯示，由組織胞漿菌感染小鼠體內取出之CD8 T 細胞胞內會 表現干擾素γ 及granzyme B 。此外，CD8 T 細胞也具有細胞毒殺的功能，能夠 毒殺含組織胞漿菌的IC-21 巨噬細胞。因此，CD8 T 細胞對於宿主抵抗胞內非病 毒之病源菌感染是相當重要的，尤其當在宿主缺乏功能性 CD4 T 細胞的情況 下。(此部分已寫成論文投稿至Journal of Immunology)Part I. Functional T cells are critical to host defense against infection. It has been reported that functional T cells as determined by their cytokine production represent antigen-specific T cells in infectious disease models. In this study, we enumerated Histoplasma-specific interferon γ -producing cells in bulk splenocyte culture and showed that infection with Histoplasma capsulatum, an intracellular pathogen of the macrophage, activated both CD4 and CD8 T cells. The magnitude of CD8 T cell response was lower than CD4 T cell, but the expansion and contraction of both cell types followed the same kinetics. Over 90% of interferon γ -producing CD4 T cells and >85% of CD8 T cells expressed CD44 hi phenotype. The strong correlation between interferon γ production and CD44 hi expression was observed not only at the peak of response but also throughout the course of infection. Moreover, a broad spectrum of V β populations responded to systemic as well as pulmonary infections, suggesting no obvious T cell receptor bias in primary immune response to histoplasmosis. While each V β population contributed to interferon γ production, several specific V β populations made up higher percentages of interferon γ -producing cells. Our study laid the groundwork for further investigations in immune response to histoplasmosis. (Accepted for publication on International Immunology, 16: 1663-1673, 2004) Part II. The contribution of CD8 T cells in host defense against histoplasmosis is minor in the CD4-T-cell-intact mouse, as it has been shown that depleting CD8 T cells delays but does not affect fungal clearance. However, it remains to be determined whether the CD8 T cells are protective in a host lacking functional CD4 T cells. In this study, MHC class II-deficient mice infected with Histoplasma kept the fungus in check for up to 16 weeks, indicating CD8 T cells are able to limit fungal replication. Ex vivo studies showed that CD8 T cells from Histoplasma-infected mice expressed both intracytoplasmic interferon-gamma and granzyme B. Furthermore, CD8 T cells exhibited cytotoxic activity against IC-21 macrophage targets containing Histoplasma. Therefore, CD8 T cells are critical for host defense against the intracellular nonviral pathogen, especially in a host lacking functional CD4 T cells. (In revision)application/pdf170889 bytesapplication/pdfzh-TW國立臺灣大學醫學院免疫學研究所CD4 T 細胞CD8 T 細胞組織胞漿菌功能性 T 細胞CD4 T cellsCD8 T cellsHistoplasmafunctional T cells[SDGs]SDG3journal articlehttp://ntur.lib.ntu.edu.tw/bitstream/246246/25366/1/922320B002178.pdf