Caspase-8信号分子对SLE患者T细胞亚群的双向调节作用研究

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.

Double regulatory effects of caspase-8 signaling on different T cell subpopulations of patients with systemic lupus erythematosus

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.