CD4~+Foxp3~+T细胞亚群在系统性红斑狼疮中的免疫抑制功能研究

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采用五色流式细胞术检测系统性红斑狼疮(systemic lupus erythematosus,SLE)患者和健康对照组的CD4+Foxp3+T细胞及其细胞亚群;以CFSE染色法分析SLE患者和健康对照组CD4+Foxp3+T细胞各亚群的免疫抑制功能。结果发现SLE组CD4+Foxp3+T细胞(占CD4+T细胞的比例)显著高于对照组(12.03%±1.523%vs 6.410%±0.4353%,t=3.790,P<0.01),但其CD4+T细胞的增殖却比对照组活跃(PI:4.052%±0.4004%vs 2.528%±0.2322%,t=3.293,P<0.05)。根据Foxp3和CD45RA表达强度的差异,可将CD4+Foxp3+T细胞清晰地分成3个亚群:CD45RA+Foxp3low(Ⅰ区)细胞、CD45RA-Foxp3high(Ⅱ区)细胞和CD45RA-Foxp3low(Ⅲ区)细胞,SLE组的Ⅰ区和Ⅲ区细胞数量显著增加(分别为t=2.123,P<0.05;t=3.462,P<0.01),而Ⅱ区细胞与对照组之间差异无统计学意义(0.6056%±0.1879%vs0.6571%±0.1764%,t=0.1999,P>0.05)。SLE患者和健康对照者的Ⅰ区和Ⅱ区细胞在体外均具有免疫抑制功能,而Ⅲ区细胞不具有该功能。SLE患者Ⅰ区细胞的免疫抑制能力弱于对照组(t=2.994,P<0.05),而Ⅱ区细胞和Ⅲ区细胞与对照组之间差异均无统计学意义。提示,SLE患者CD4+Foxp3+T细胞比例升高而免疫抑制功能下降,可能是两大原因造成了这种数量和功能的不一致性:①SLE患者CD4+Foxp3+T细胞数量增加主要由于Ⅲ区细胞增多所致,而这区细胞不具有免疫抑制功能;②在SLE患者,具有免疫抑制功能的Ⅰ区细胞的抑制能力明显减弱。 CD4 + Foxp3 + T cells and their cell subsets were detected by flow cytometry in patients with systemic lupus erythematosus (SLE) and healthy controls. The levels of CD4 + Foxp3 in SLE patients and healthy controls were analyzed by CFSE staining + T cell subsets of the immunosuppressive function. The results showed that the proportion of CD4 + Foxp3 + T cells in SLE group was significantly higher than that in control group (12.03% ± 1.523% vs 6.410% ± 0.4353%, t = 3.790, P <0.01) T cell proliferation was more active than the control group (PI: 4.052% ± 0.4004% vs 2.528% ± 0.2322%, t = 3.293, P <0.05). According to the difference of Foxp3 and CD45RA expression intensity, CD4 + Foxp3 + T cells can be clearly divided into three subgroups: CD45RA + Foxp3low (Ⅰ), CD45RA-Foxp3 high (Ⅱ) and CD45RA-Foxp3low (P <0.05). There was no significant difference between cells in group Ⅱ and control group (0.6056, t = 2.123, P < % ± 0.1879% vs0.6571% ± 0.1764%, t = 0.1999, P> 0.05). The cells in zone I and zone II of SLE patients and healthy controls all have immunosuppressive function in vitro, but cells in zone III do not have this function. The immunosuppressive capacity of cells in area I of SLE patients was weaker than that of the control group (t = 2.994, P <0.05), while there was no significant difference between the cells in area II and the cells in area III. These results suggest that the increased proportion of CD4 + Foxp3 + T cells in SLE patients and the decreased immunosuppressive function may be caused by two major causes of this inconsistency in number and function. ① The increase in the number of CD4 + Foxp3 + T cells in SLE patients is mainly attributed to the number of cells in zone III Increase in the area, but this area does not have immunosuppressive cells; ② in patients with SLE, with immunosuppressive function of cells in zone Ⅰ inhibition was significantly reduced.
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