Habib H M, Taher T E, Isenberg D A, Mageed R A
Centre for Rheumatology, University College London School of Medicine, London, UK.
Scand J Rheumatol. 2009 Mar-Apr;38(2):112-20. doi: 10.1080/03009740802409496.
To determine the effect of inflammation through exposure to tumour necrosis factor (TNF)alpha on T lymphocytes in patients with systemic lupus erythematosus (SLE).
We studied the effect of TNFalpha on T-lymphocyte apoptosis in patients with SLE, rheumatoid arthritis (RA), and in healthy controls. Apoptosis of CD4 and CD8 T lymphocytes and naive and memory subpopulations was determined by flow cytometry using 7-amino-actinomycin D (7AAD) and propidium iodide (PI). In SLE, apoptosis was studied in patients with active and inactive disease and in patients on different medications.
TNFalpha enhanced apoptosis of anti-CD3-activated T lymphocytes. The percentage of apoptotic cells was significantly higher in T lymphocytes from patients with SLE than RA patients and healthy controls. After 3 days of culture, 38% of CD4+ and 37% of CD8+ cells from SLE patients underwent apoptosis in the presence of TNFalpha compared with 25% CD4+ and 26% CD8+ T cells from the controls (p<0.001). In healthy controls, more memory than naive T lymphocytes underwent apoptosis. By contrast, in patients with SLE, more naive T cells underwent apoptosis with TNFalpha (p<0.01). Enhanced apoptosis of T cells in SLE was independent of disease activity or medication. Finally, inhibition experiments showed that apoptosis in the presence of TNFalpha was only partly blocked with anti-Fas ligand (FasL) antibody.
This study demonstrates that T lymphocytes in patients with SLE are more prone to apoptosis in the presence of TNFalpha than T lymphocytes from healthy controls. Defects in TNFalpha signalling pathways rather than distribution of TNF receptors (TNFRs) probably explain the enhanced apoptosis in SLE.
通过暴露于肿瘤坏死因子（TNF）α来确定炎症对系统性红斑狼疮（SLE）患者T淋巴细胞的影响。
我们研究了TNFα对SLE患者、类风湿关节炎（RA）患者及健康对照者T淋巴细胞凋亡的影响。使用7-氨基放线菌素D（7AAD）和碘化丙啶（PI），通过流式细胞术测定CD4和CD8 T淋巴细胞以及初始和记忆亚群的凋亡情况。在SLE患者中，研究了疾病活动期和非活动期患者以及使用不同药物治疗的患者的凋亡情况。
TNFα增强了抗CD3激活的T淋巴细胞的凋亡。SLE患者T淋巴细胞中的凋亡细胞百分比显著高于RA患者和健康对照者。培养3天后，在TNFα存在的情况下，SLE患者中38%的CD4+细胞和37%的CD8+细胞发生凋亡，而对照组中CD4+细胞和CD8+细胞的凋亡率分别为25%和26%（p<0.001）。在健康对照者中，记忆T淋巴细胞比初始T淋巴细胞更容易发生凋亡。相比之下，在SLE患者中，TNFα作用下更多的初始T细胞发生凋亡（p<0.01）。SLE患者T细胞凋亡增强与疾病活动或药物治疗无关。最后，抑制实验表明，TNFα存在时的凋亡仅部分被抗Fas配体（FasL）抗体阻断。
本研究表明，与健康对照者的T淋巴细胞相比，SLE患者的T淋巴细胞在TNFα存在时更容易发生凋亡。TNFα信号通路的缺陷而非TNF受体（TNFRs）的分布可能解释了SLE中凋亡增强的现象。
