Division of Rheumatology - Escola Paulista de Medicina, UNIFESP, Universidade Federal de São Paulo, Rua Botucatu 740, SP, 04023-062, São Paulo, Brazil.
Adv Rheumatol. 2023 Aug 16;63(1):40. doi: 10.1186/s42358-023-00321-3.
Serum from systemic lupus erythematosus (SLE) patients has been shown to induce T-lymphocyte (TL) apoptosis. Given that different cells of the immune system display different sensitivity to apoptosis, we set to evaluate the in vitro effect of SLE serum on regulatory T-cells (Treg), Th17, Th1 and Th2 from SLE patients and healthy controls.
Peripheral blood mononuclear cells from SLE patients or normal controls were exposed to a pool of sera from SLE patients or normal controls. Annexin V was used to label cells in apoptosis or necrosis. Annexin V-labeled Treg, Th17, Th1 and Th2 cells were determined using flow cytometry.
Total CD3 + and CD4 + cells from SLE patients showed higher frequency of spontaneous apoptosis/necrosis, whereas Th1 cells from SLE patients presented reduced spontaneous apoptosis/necrosis rate as compared with cells from controls. Incubation with SLE serum induced increased frequency of apoptotic/necrotic CD3 + , CD4 + and Th2 cells from normal controls or from SLE patients as compared with cultures incubated with normal human serum (NHS) or without human serum at all. Incubation with SLE serum did not increase the apoptosis/necrosis rate in Th1 or Th17 cells. Treg cells from SLE patients were more prone to apoptosis/necrosis induced by SLE serum than Treg cells from normal individuals. Th1, Th2, and Th17 cells presented increased apoptosis rates in cultures without human serum.
Our findings indicate that the serum of patients with active SLE stimulates apoptosis of CD4 + T cells in general and exhibit differentiated effects on CD4 + T-cell subsets.
已证实系统性红斑狼疮 (SLE) 患者的血清可诱导 T 淋巴细胞 (TL) 凋亡。鉴于免疫系统的不同细胞对凋亡的敏感性不同，我们评估了 SLE 患者和健康对照者的血清对调节性 T 细胞 (Treg)、Th17、Th1 和 Th2 的体外作用。
将 SLE 患者或正常对照者的外周血单个核细胞暴露于 SLE 患者或正常对照者的血清混合液中。用 Annexin V 标记凋亡或坏死的细胞。用流式细胞术测定 Annexin V 标记的 Treg、Th17、Th1 和 Th2 细胞。
与对照者相比，SLE 患者的总 CD3+和 CD4+细胞表现出更高频率的自发性凋亡/坏死，而 SLE 患者的 Th1 细胞则表现出较低的自发性凋亡/坏死率。与孵育正常人类血清 (NHS) 或无人类血清相比，孵育 SLE 血清可诱导正常对照者或 SLE 患者来源的 CD3+、CD4+和 Th2 细胞凋亡/坏死频率增加。SLE 血清并未增加 Th1 或 Th17 细胞的凋亡/坏死率。与正常个体的 Treg 细胞相比，SLE 患者的 Treg 细胞更易受到 SLE 血清诱导的凋亡/坏死。在无人类血清的培养物中，Th1、Th2 和 Th17 细胞的凋亡率增加。
我们的发现表明，活动期 SLE 患者的血清一般可刺激 CD4+T 细胞凋亡，并对 CD4+T 细胞亚群表现出不同的作用。
