在慢性病毒性肝炎病人肝臟浸潤細胞的共同抑制性分子和共同刺激性分子表現量之研究

The Study of the Expression of Co-inhibitory and Co-stimulatory Molecules in Hepatic Infiltrating Lymphocytes in Chronic Viral Hepatitis

萬川(Chuan Wan)

指導教授 ： 許秉寧

國立臺灣大學/醫學院/免疫學研究所/碩士(2007年)

https://doi.org/10.6342/NTU.2007.00481

摘要

肝臟的病毒感染是一個全球性的嚴重問題。全球有數以百萬計的人感染病毒性肝炎，而且其中許多人會進展成為慢性病毒性肝炎。至於造成持續地病毒感染和不良的免疫反應的病因仍待進一步地闡明。近來，一些研究揭露了共同抑制因子(co-inhibitory molecules)在減損病毒特異性淋巴球功能的重要性。而化學性激素接受器在近幾年也被發現在召集淋巴球回流至特異的器官上佔有重要的角色。
有鑑於此，首先，我們試著找出共同信號分子在周邊淋巴球和肝臟浸潤淋巴球上的表現是否有任何的不同。接著，我們試著找出這些分子之間的相關性。化學性激素接受器CXCR6，一種已知會召集淋巴球回流至發炎肝臟的分子，它們在慢性病毒性肝炎病人淋巴球上的表現量及它們和共同抑制性或共同剌激性分子間的相關性也是這次研究的目標。
在這次研究中，我們發現相較於周邊血淋巴球，肝臟浸潤淋巴球PD-1分子的表現量有顯著的增加，而CD28分子的表現量有明顯的降低。在肝臟浸潤淋巴球中，化學性激素接受器CXCR6表現量也有顯著的增加，同時在具化學性激素接受器CXCR6表現的肝臟浸潤淋巴球中，帶有PD-1分子的細胞數也有增加。此外，我們觀察到：相較於周邊血淋巴球，肝臟浸潤淋巴球的CD127表現(淋巴球的耗竭性標記)，有明顯降低的現象。由以上的結果可知：相對於周邊血淋巴球，在肝臟浸潤淋巴球較高的PD-1表現和較低的CD28表現，可能暗示著慢性病毒性肝炎的肝浸潤淋巴球在功能上是受損的。另外，具化學性激素接受器CXCR6表現的肝臟浸潤淋巴球中，帶有PD-1分子的細胞數也有增加。可能暗示召集回流至發炎肝臟的淋巴球在功能上是受到抑制的。

關鍵字

周邊血細胞 ； 肝浸潤細胞 ； 共同抑制性分子 ； 共同刺激性分子

並列摘要

Viral infection in liver is a serious problem worldwide. There are millions of people infected with viral hepatitis and many of those progress to chronic virus infection of the liver. The etiology of persistent viral infection and poor immune response to clear these viruses remains for further elucidation. Recently some studies shed light on the importance of co-inhibitory molecules in compromising the function of virus specific cytotoxic T cells. Chemokine receptors also are known to play important roles in the homing of lymphocytes into the specific organs.
First, we tried to find out whether there is any difference in the expression of co-stimulatory/co-inhibitory molecules in peripheral blood lymphocytes and hepatic infiltrating lymphocytes. We then evaluated the correlation between these molecules. A chemokine receptor CXCR6, a recruiting molecule for lymphocytes to inflamed liver, was studied for its expression in chronic viral hepatitis patients and for the relationship between its expression and co-stimulatory/co-inhibitory molecules.
In this study, we found that PD-1 molecule expression was increased and CD28 molecule expression was decreased in the liver infiltrating lymphocytes (LILs) compared to their expressions in the peripheral blood lymphocytes (PBLs). There is an increase of CXCR6 expression in LILs. In hepatic infiltrating lymphocytes, the number of PD-1+CXCR6+CD3+T cells is increased compared with the number of these cells in PBLs. There was a low expression level of CD127, the marker of exhausted lymphocytes, in the LILs compared to the PBLs. The higher expression of PD-1 and lower CD28 expression in liver infiltrating lymphocytes might be suggestive of the impairment of LIL function in chronic hepatitis. Besides, the number of PD-1+CXCR6+CD3+ T cells is increased in LILs. This finding may imply the recruited hepatic infiltrating lymphocytes have impaired function.

並列關鍵字

PBLs ； LILs ； co-inhibitory molecules ； co-stimulatory molecules

參考文獻

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