Expression Of Caspase-3 And TRAIL Receptors In CD4 And CD8 T Cells From Systemic Lupus Erythematosus Patients

Objective:Systemic lupus erythematosus (SLE) is a typic autoimmune disease characterized by the production of antibodies to components of the cell nucleus in association with a diverse array of clinical manifestations. The basic pathological features of SLE are immune complexs deposition,vasculitis and vasculopathy,which lead to morphological changes and dysfunction with tissues and organs. Investigations have demonstrated that increased apoptosis and insufficient clearance of apoptosis cells are keys in SLE formation and progression. Signaling via cell-surface receptors of the tumor necrosis factor receptor family is considered an important trigger mechanism to activate the cell's apoptosis. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is one of several members of the TNF gene superfamilies that induce apoptosis through engagement of death receptors. The TRAIL receptors mainly include the death-inducing receptors TRAIL receptor 1 (TRAIL-Rl,also referred to as DR4) and TRAIL-R2 (also referred to as DR5); and the truncated TRAIL receptors TRAIL-R3 (also referred to as DcR1, TRID2or LIT)and TRAIL-R4 (also referred to as DcR2). Interactions between TRAIL and death-inducing TRAIL receptors will activate the effector caspases downstream and lead to the apoptosis of the transformed cells and tumor cells.Caspase-3 is an important activated downstream death protease.To explore the mechanism of the apoptosis of T cells.Here, we studied the expression of the caspase-3 and TRAIL receptors in human CD4 and CD8 T cells from SLE patients respectively.Methods: 20ml of peripheral blood from 20 SLE patients and 10 healthy controls were collected, and CD4 and CD8 T cells were separated by using magnetic cell sorting system(MACS).Then RT-PCR was used to test the expression of the caspase-3 and TRAIL receptors in CD4 and CD8 T cells from SLE patients and healthy controls.Results:1, CD4 and CD8 T cells were separated successfully from 20 SLE patients and 10 healthy controls.Results of flow cytometry showed that all the purities of the CD4 and CD8T cells were above 90%.2, The comparison of the CD4and CD8 T cells showed that the numbers of CD4 T cells in the peripheral blood of SLE patients ,SLE patients whose SLEDAKIO and SLE patients whose SLEDAI>10 were lower than those of healthy controls (SLE, p=0.001; SLEDAK10,p=0.021;SLEDAI>10,p=0.000).The numbers of CD4 T cells of the SLE patients whose SLEDAKIO were significantly higher than those of SLE patients whose SLEDAI>10(p=0.008).The numbers of CD8 T cells in the peripheral blood of SLE patients whose SLEDAI>10 were lower than those of healthy controls (p=0.016).The ratios of CD4/CD8 of the SLE patients and SLE patients whose SLEDAI>10 were lower than those of healthy controls(SLE,P=0.046;SLEDAI>10, p=0.019).3 > There were no significant differences in the expression of caspase-3 and TRAIL receptors in the CD4 T cells of the peripheral blood between SLE patients and healthy controls.The CD8 T cells from the SLE patients showed higher caspase-3 and TRAIL-R2 expression than healthy controls, the expressions also correlated with activity of the disease (caspase-3:SLEDAI>10,P=0.004;SLEDAI<10, P=0.021.TRAIL-R2:SLE,P=0.024; SLEDAI>10,P=0.011).Conclusions: The numbers of CD4 T cells in the peripheral blood and CD4 /CD8 ratio of SLE patients were lower than those in healthy controls. The numbers of CD4 T cells in the peripheral blood from the SLE patients whose SLEDAKIO were significantly higher than those in SLE patients whose SLEDAI>10,and the numbers of CD8 T cells and CD4 /CD8 ratio of SLE patients whose SLEDAI>10 were lower than healthy controls.The death domain-containing and decoy receptors were co-expressed in vast majority of CD4 and CD8 T cells of SLE patients and normal controls.The decoy receptors TRAIL-R3 and TRAIL-R4 had no significant difference in the expression on healthy cells and CD4^ CD8 T cells of the SLE patients.Conversely,in CD8 T cells from SLE patients,there existed increased expression of caspase-3 and functional TRAIL-R2 ,and the expressions correlated with activity of the disease,which might represent the underlying basis for cells to undergo TRAIL-mediated apoptosis.