Background T cells from SLE patients have higher spontaneous apoptotic rate than that from healthy donors. The appearance of nucleosomes from these apoptotic cells in circulation may induce the production of autoantibodies and subsequently cause organ damage. Meanwhile, an aberrant autophagy of T cells from SLE patients has been observed.
Objectives To investigate the relationship between apoptosis and autophagy of T cells from SLE patients, and to find out whether umbilical cord derived mesenchymal stem cells (UC-MSCs), previously shown to inhibit autoantibody production after in vivo transplantation, act through the regulation of T cell apoptosis and autophagy.
Methods Peripheral blood mononuclear cells (PBMCs) were isolated from SLE patients and healthy donors, and then CD3+T cells were purified with microbeads and cultured under stimulation with anti-CD3/28 antibodies in the presence or absence of autophagy inhibitor 3-MA (5mM for 6h) or activator rapamycin (50nM for 48h). To find out the effect of MSCs on T cell autophagy, UC-MSCs were cocultured with T cells at the ratio of 1:10. Apoptosis and autophagy level were measured by flow cytometry with the detection of Annexin V and LC3IIB respectively. Anti-dsDNA antibodies were quantificated by ELISA.
Results T cells from SLE patients had high apoptotic level (0.71±0.13% vs. 1.78±0.32% for CD4+T, p=0.05; 1.82±0.23% vs. 3.58±0.32% for CD8+T, p<0.01) and increased autophagy rate (3.58±0.07% vs. 5.25±0.22% for CD4+T; 5.01±0.09% vs. 7.52±0.26% for CD8+T, both p<0.001) compared with those from normal controls. The apoptotic rate of CD8+T cells was significantly correlated with serum anti-dsDNA antibody levels (r=0.755, p<0.05). Inhibition of autophagy with 3-MA decreased the apoptotic rate of T cells (32.1±9.4% vs. 20.4±5.2%, p<0.05), whereas activation of autophagy with rapamycin increased the apoptotic rate (33.1±10.0% vs. 65.3±10.1%, p<0.001). UC-MSCs could decrease both T cell autophagy (36.4±6.3 vs. 22.5±2.4 for CD4+T; 39.2±5.4 vs. 27.2±1.9 for CD8+T, both p<0.05) and T cell apoptosis (49.1±5.7% vs. 22.2±2.6% for CD4+T; 53.2±2.3% vs. 23.3±2.4% for CD8+T, both p<0.05).
Conclusions T cells from SLE patients have high spontaneous apoptotic rate, which is related to the aberrant autophagy. UC-MSCs may inhibit T cell apoptosis through the modulation of autophagy.
Disclosure of Interest : None declared
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