伍安怡2018-07-092018-07-092005http://ntur.lib.ntu.edu.tw//handle/246246/25374在宿主防禦及黏膜免疫反應中 T 細胞扮演重要角色。在呼吸道感染中，T 細胞被活化並在肺臟周圍淋巴結增生，分化的 T 細胞由淋巴結移至肺臟以執行 功能。本實驗室的研究發現，組織胞漿菌肺部感染之小鼠引發第一型 T 細胞反 應，並在感染之肺部形成有細胞浸潤的肉芽腫。研究曾指出 IP-10 蛋白質表現 在肺結核病人的呼吸道。因 IP-10 及其他干擾素γ 可誘導之細胞趨化素 Mig 和 I-TAC 對於吸引活化T 細胞，尤其是 Th-1 細胞，扮演重要角色，我們假設在 活化的 Th-1 細胞上表現之 CXCR3 在肺部感染模式中指導分化的 T 細胞由 肺臟周圍淋巴結遷移至肺臟。我們利用組織胞漿菌肺部感染模式來研究與 Th-1 相關之細胞趨化素的表 現情形。同時利用 CXCR3 -/- 小鼠來研究活化的 Th-1 細胞及其他免疫細胞由淋 巴結至器官的遷移。我們的研究發現，肺部感染組織胞漿菌後病菌的清除並未受 到 CXCR3 缺乏而有明顯影響。然而在 CXCR3 缺乏小鼠中，在肺臟周圍淋巴 結中的 NK 細胞數目明顯減少，顯示肺部感染時 NK 細胞由周圍淋巴結遷移至 肺臟是與 CXCR3 有關的。在全身性感染中，去除 CXCR3 配體 IP-10 及 CCR5 配體 RANTES 的小鼠分別在感染第7 天及第14 天有較高的病菌負荷 量。這些研究結果顯示，IP-10 參與和 NK 細胞相關之早期組織胞漿菌炎，而 RANTES 對於感染晚期與活化 T 細胞遷移吸引相關之病菌清除有貢獻。In respiratiory infections, activated T cells are recruited into the lungs where they exert effector functions. The T cells are activated and expand in the lung-associated lymph nodes following a respiratory infection. The differentiated T cells migrate from the lymph nodes to the lung. Our study showed that mouse with pulmonary histoplasmosis mount a type 1 T cell response, and granuloma was formed in infected lungs with infiltrating cells. The expression of IP-10 protein is reported in the airway of tuberculosis patients. Since IP-10 and other IFN-γ inducible chemokines, Mig and I-TAC are important in the recruitment of activated T cells, especially Th-1 cells, we hypothesize that CXCR3 expression on activated Th1 cells in the pulmonary infection model directs the migration of differentiated T cell from lung-associated lymph nodes to the lung. Using pulmonary histoplasmosis animal model, we studied the kinetics of the expression of Th1-associated chemokines in the infection. In addition, CXCR3 -/- mice were used to study trafficking of activated Th1 T cells as well as other immune cells from lymph node to their target organ. We found that fungal clearance in pulmonary histoplasmosis is not significantly affected by CXCR3 deficiency. However, in CXCR3-deficient mice, the number of NK cells is reduced in the draining lymph node of lungs, indicating that NK cell migration to the lymph node in pulmonary infection is CXCR3-dependent. In systemic infection, depletion of CXCR3 ligand IP-10 and CCR5 ligand RANTES in wild type mice increased the fungal burdens at day 7 and day 14, respectively, after infection. The results indicate that IP-10 is involved in the early phase of histoplasmosis when NK cells are involved in host defense while RANTES contributes to the later phase of infection when activated T cells are recruited for fungal clearance.application/pdf332917 bytesapplication/pdfzh-TW國立臺灣大學醫學院免疫學研究所[SDGs]SDG3journal articlehttp://ntur.lib.ntu.edu.tw/bitstream/246246/25374/1/932320B002076.pdf