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Caspase-8信号分子对SLE患者T细胞亚群的双向调节作用研究 被引量:1

Double regulatory effects of caspase-8 signaling on different T cell subpopulations of patients with systemic lupus erythematosus
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摘要 目的分析SLE患者外周血T细胞内活化Caspase-8、Caspase-3和T细胞膜上Fas、CD69以及外周血中Foxp3+CD4+CD25+调节性T细胞的表达,探讨他们在SLE患者免疫失衡中的作用。方法用流式细胞术检测活化Caspase-8、Caspase-3和Fas、CD69以及Foxp3+CD4+CD25+Treg的表达。结果与健康对照相比,SLE患者外周血CD3+CD4+T细胞上Fas表达显著升高(P<0.05),无论稳定期或活动期SLE患者CD3+CD4+T细胞和CD3+CD8+T细胞中活化Caspase-8的表达均显著增加(P<0.05),且稳定期和活动期SLE患者CD3+CD8+T细胞中活化Caspase-8的表达高于其在CD3+CD4+T细胞中的表达(P<0.05);但是仅活动期SLE患者T细胞内活化Caspase-3表达增加(P<0.05),同时稳定期和活动期SLE患者CD3+CD4+T细胞中活化Caspase-3的表达高于其在CD3+CD8+T细胞中的表达(P<0.05)。同时SLE患者CD3+CD8+T细胞上CD69表达率升高(P<0.05),但是CD69在CD3+CD4+T细胞上的表达率与健康对照相比无显著性差异(P>0.05)。SLE患者外周血中Foxp3+CD4+CD25+Treg比例显著低于健康对照(P<0.05)。结论Caspase-8介导的信号事件同时参与诱导SLE患者淋巴细胞的凋亡与活化,促使SLE患者体内免疫反应向Th2极化,同时由于SLE患者外周血中Foxp3+CD4+CD25+Treg表达降低所介导的免疫抑制效应缺陷,他们共同作用促使SLE患者外周免疫平衡障碍。 Objective To analyze the intracellular expression of active Caspase-8/Caspase-3 and the expressions of Fas and CD69 in the T cells from SLE patients, and to detect the frequency of Foxp3^+ CD4^+ CD25^+ regulatory T cells in the peripheral blood from SLE patients, so as to discuss their roles in the immune imbalance of SLE. Methods Flow cytometry was used to determine the expression percentages of Fas, CD69, activated Caspase-8, Caspase-3, and the frequency of Foxp3^+ CD4^+ CD25^+ Treg. Results Compared with healthy control, the percentage of Fas expressed on the surface of CD3^+ CD4^+ T cells from SLE patients increased significantly ( P 〈 0.05), and the intracellular expression of active Caspase-8 in both CD3^+ CD4^+ T cells and CD3^+ CD8^+ T cells from SLE patients was higher ( P 〈 0.05), particularly higher in CD3^+ CD8^+ T cells than in CD3^+ CD4^+ T cells from both SLE patients and healthy controls (P 〈 0.05). But the intracellular expression of active Caspase-3 was only higher in CD3^+ CD4^+ T cells and CD3^+ CD8^+ T cells of SLE patients in active phase( P 〈 0.05), and the intracellular expression of active Caspase-3 was higher in CD3^+ CD4^+ T cells than that in CD3^+ CD8^+ T cells from SLE patients and healthy controls ( P 〈 0.05). The expression of CD69 on the surface of CD3^+ CD8^+ T cells increased significantly ( P 〈 0.05), but there was no difference in the expression of CD69 on the surface of CD3^+ CD4^+ T cells between SLE patients and health controls. The percentage of Foxp3 ^+ CD4^+ CD25^+ Treg decreased significantly in the peripheral blood from SLE patients ( P 〈 0.05). Conclusion Signaling events mediated by Caspase-8 play roles in both the apoptosis and activation of T lymphocytes, which promoted the Th2 polarization of immune reaction. The impairment of the inhibitory effects mediated by decreasing Foxp3^+ CD4^+CD25^+ Treg contributes to the imbalance of peripheral homeostasis in SLE.
出处 《免疫学杂志》 CAS CSCD 北大核心 2007年第6期675-680,共6页 Immunological Journal
基金 国家自然科学基金项目(30670819)l 四川省科技攻关项目(2006Z09-037)
关键词 CASPASE-8 Caspase-3 Fas CD69 FOXP3 凋亡 SLE 调节性T细胞 Caspase-8 Caspase-3 Fas CD69 Foxp3 Apoptosis Systemic lupus erythematosus Regulatory T cells
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