口腔扁平苔癬病人周邊血液毒殺性淋巴球之特性分析

Functional characterization of peripheral blood CD8+ T cells from patients with oral lichen planus

胡渝翔(Yu-Shiang Hu)

指導教授 ： 賈景山

國立臺灣大學/醫學院/免疫學研究所/碩士(2011年)

https://doi.org/10.6342/NTU.2011.02875

摘要

口腔扁平苔癬是一種病因仍不明瞭之口腔黏膜自體免疫疾病。國外研究發現從病人病灶部位分離出之CD8+ T 細胞對自體口腔黏膜的角質層細胞具有毒殺能力。最近的研究指出紅斑性狼瘡病人體中的CD8+ T細胞有較高的IL-7受體表現。因此本研究探討在口腔扁平苔癬病人中的周邊血液CD45RA- CD8+ T細胞與CD45RA+ CD8+ T細胞IL-7受體表現以及製造細胞激素的能力。分選出之周邊血液IL-7R+ CD45RA- CD8+ T 細胞利用流式細胞儀染色分析或是分離出之細胞以anti-CD3加上自體抗原呈現細胞共同培養並以ELISA測定之。病人的CD8+ T 細胞相對於控制組有較高的IFN-γ以及granzyme B表現量但FasL在病人與控制組並無差異。病人的CD8+ T 細胞含有高量IFN-γ以及granzyme B 被認為具有毒殺目標細胞的能力。事實上，在細胞毒殺能力的實驗中，病人的CD8+ T 細胞有較高的毒殺能力。此外病人CD8+ T 細胞有較高的IL-7受體表現與較高的IFN-γ 和 granzyme B 在病人的CD8+ T 細胞具高度正相關，可能是因為IL-7受體能幫助記憶性T細胞數量的恆定。另一方面，病人有較高的CD4+ IL-17細胞表現而且同樣的與高量的IFN-γ CD8+ T 細胞是有高度正相關，而且CD4+ T細胞分泌較少的IL-10。從以上的發現顯示周邊血液記憶性CD8+ T 細胞參與口腔扁平苔癬中的致病機轉而且可能是一項造成疾病復發的風險因素。

關鍵字

口腔扁平苔癬 ； 毒殺性淋巴球

並列摘要

Oral lichen planus (OLP) is an autoimmune oral mucosal disease of unknown etiology. In vitro study shows that CD8+ T Cells from Oral lichen planus (OLP) patient’s lesion sites are cytotoxic to autologous keratinocytes. A recent report implicated that CD8+ T cells from patients with recurrent SLE exhibited up-regulated IL-7R. We examined the expression IL-7R of peripheral CD45RA- CD8+ T cells and CD45RA+ CD8+ T cells in patient with OLP and analyzed cytokine production. Peripheral blood IL-7R+ CD45RA- CD8+ T cells were sorted and the cytokine profiles were detected by flow cytometry, or ELISA after stimulation with anti-CD3 mAb in the presence of autologous APCs. Killing activity will be tested using mouse Mastocytoma P815 cell line. CD8+ T cells from OLP patients had increased IFN-γ production in contrast to healthy donor CD8+ T cells whereas expression of FasL was similar. The CD8+ T cells in OLP patient had increased IFN-γ production and granzyme B were able to trigger target cells apoptosis, in addition, using P815 cytotoxicity assay patient CD8+ T cells had higher killing ability, suggested that CD8+ T cells had enhanced effector function. CD8+ T cells in patient had higher IL-7R expression that correlated with level of IFN-γ production and granzyme B expression, to maintain memory phenotype of CD8+ T cells. On the other hand, higher frequency of IL-17 producing CD4+ T cells was also observed and correlated with increased CD8 IFN-γ production. IL-10 production from CD4+ T cells cultured supernatant was lower than healthy donors. Taken together, these data suggested that the overexpression of IFN-γ in peripheral blood memory CD8+ T cells may contribute to the immunopathogenesis of OLP and would be a risk factor of this relapsing disease.

並列關鍵字

oral lichen planus ； CD8+ T cells

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