全身性紅斑狼瘡病人CD4+CD25+調節性T細胞之特性分析

The characterization of CD4+CD25+ regulatory T cells in systemic lupus erythematosus

李曉婷(Hsiao-Ting Li)

指導教授 ： 孫昭玲

高雄醫學大學/醫學院/醫學研究所/碩士(2007年)

摘要

前言：全身性紅斑性狼瘡（systemic lupus erythematosus；SLE）是種造成多器官系統受損的自體免疫疾病，主要是因為過度活化的B和T細胞無法被調控和喪失免疫耐受性；CD4+CD25+ T細胞（regulatory T cells；Treg）在維持自體免疫耐受性和調節免疫反應上扮演著關鍵角色，並且會特異性表現Foxp3，而人類CD4+Foxp3+ T細胞可分成兩群，一群為CD25hi的natural Treg（nTreg），另一群為CD25表現量不一定的adaptive Treg（aTreg）；本論文主要目的是去偵測紅斑性狼瘡病人調節性T細胞的體內比例及其功能。
實驗方法：以流式細胞儀分析CD4+Foxp3+ T細胞的比例和表現型；利用anti-CD3抗體活化CD4+CD25hiFoxp3+和naïve T細胞，進而評估CD4+CD25hiFoxp3+ T細胞的抑制能力。
結果：我們發現在active SLE病人周邊血中，CD4+ Foxp3+ T細胞無論是否表現CD25，其比例都明顯比正常人或僵直性脊椎炎（ankylosing spondylitis；AS）病人具統計意義的增加，但是由於病人effector T細胞的比例也明顯增加，所以CD4+CD25+Foxp3+與effector T細胞比例是具有統計意義的下降；細胞表面分子的分析發現，紅斑性狼瘡病人的CD4+Foxp3+ T細胞會表現GITR及CTLA-4的細胞比例較正常人低，而CD4+CD25hiFoxp3+ T細胞的in vitro功能則為正常。
結論：我們的實驗顯示，紅斑性狼瘡病人nTreg的in vitro功能正常，而經過表面分子分析推測病人的aTreg可能有問題。這些研究將有助於進一步了解全身性紅斑性狼瘡的致病機轉和開發新的臨床治療方式。

關鍵字

全身性紅斑性狼瘡 ； CD4+CD25hi調節性T細胞

並列摘要

Objective. Systemic lupus erythematosus (SLE) is a multiorgan autoimmune disease that are attributed to inappropriate regulation of hyperactivated B and T cells and loss of immune tolerance. CD4+CD25hi regulatory T cells (Treg), expressing the lineage marker Foxp3, play key roles in the maintenance of immunologic self-tolerance and regulation of immune responses. There is the existence of two subsets of human CD4+Foxp3+ Treg. One is natural Treg (nTreg) which can express high level of CD25, the other is adaptive Treg which the level of CD25 expression is variable. The aim of this study was to examine the phenotype and function of CD4+Foxp3+ T cells in patients with SLE.
Method. The frequency and phenotype of CD4+Foxp3+ Treg were determined by flow cytometry. The suppressive ability of regulatory T cells were assessed by CD4+CD25hiFoxp3+ and naïve T cells cocultured with anti-CD3 monoclonal antibodies and antigen-presenting cells.
Results. Our data shows that the percentage of CD4+Foxp3+ T cells regardless of CD25 expression in active SLE patients was more significantly increased than that in normal controls and ankylosing spondylitis (AS). However, the ratio of CD4+CD25+Foxp3+ T cells versus effector T cells in SLE patients was significantly decreased. Accroding to phenotypic analysis, the percentage of GITR+ and CTLA-4+ cells in CD4+Foxp3+ T cells was significantly decreased in SLE patients compared with that in normal donors. The in vitro suppressive function of CD4+CD25hiFoxp3+ T cells was not significantly difference between SLE patients and normal controls.
Conclusion. Our data shows that the in vitro suppressive function of nTreg cells is normal compared with healthy donors. However, the defective expression of GITR and CTLA-4 in CD4+Foxp3+ T cells suggests the impaired function of aTreg in patients with SLE. These finding will help us understanding the pathogenesis of SLE and opening new strategies for clinical therapy.

並列關鍵字

Systemic lupus erythematosus ； CD4+CD25hi regulatory T cell

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