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目的研究 CD28、CTLA-4在再生障碍性贫血(AA)免疫发病机制中的可能作用。方法以流式细胞术分别分析23例发病期 AA、10例恢复期 AA 患者和15名正常人骨髓细胞中 CD3~+CD4~+T 细胞上 CD28、CTLA-4表达率,Th1、Th2细胞比例,评价 CD28、CTLA-4表达与 Th1/Th2、中性粒细胞绝对值(ANC)之间的关系。结果①正常对照组 CD3~+CD4~+T 细胞上 CD28、CTLA-4表达率及CD28~+/CTLA-4~+比值分别为(31.40±10.83)%、(2.45±1.30)%、17.02±13.44,AA 患者发病期分别为(39.84±10.89)%、(1.43±0.67)%、43.04±37.61,AA 患者恢复期分别为(22.00±9.08)%、(3.46±2.26)%、10.49±7.80;与正常对照组比较,AA 患者发病期 CD28显著升高(P0.05)。②正常对照组 Th1、Th2细胞、Th1/Th2比值分别为(4.21±2.11)%、(1.99±1.27)%、2.46±1.28,AA 发病期为(11.13±4.96)%、(2.46±1.65)%、5.20±1.98,恢复期分别为(5.39±4.29)%、(2.53±2.41)%、2.87±1.43;与正常对照组比较,AA 发病期 Th1增高,Th1、Th2平衡向 Th1偏移(P 值均<0.01),恢复期与正常对照组比较,差异无统计学意义。③AA 患者 CD28~+/CTLA-4~+比值与 Th1/Th2比值呈正相关(P<0.05),ANC 与 CD3~+CD4~+CD28~+T 细胞数呈负相关(P<0.01),与 CD3~+CD4~+CTLA-4~+T 细胞数呈正相关(P<0.01)。结论①AA 发病期患者骨髓 CD4~+T 细胞表面共刺激分子表达异常,CD28升高,而 CTLA-4下降,AA 患者骨髓 T 细胞处于“预激活”状态;②CD28/CTLA-4比值与 Th1/Th2比值呈正相关提示:CD28、CTLA-4表达失衡可引起 Th 细胞格局偏移,Th1型细胞增多。③ANC 和 CD28、CTLA-4间相关分析进一步说明CD28、CTLA-4与 AA 的发生、发展有关。
Objective To investigate the possible role of CD28 and CTLA-4 in the pathogenesis of aplastic anemia (AA). Methods The expressions of CD28 and CTLA-4 on CD3 + CD4 + T cells in 23 patients with AA, 10 AA patients and 15 normal human bone marrow cells were analyzed by flow cytometry. The proportion of Th1 and Th2 cells , Evaluate the relationship between CD28, CTLA-4 expression and Th1 / Th2, neutrophil absolute value (ANC). Results ① The positive rates of CD28, CTLA-4 and CD28 ~ + / CTLA-4 ~ + on CD3 ~ + CD4 ~ + T cells in normal control group were (31.40 ± 10.83)%, (2.45 ± 1.30)% and The incidence of AA patients was (39.84 ± 10.89)%, (1.43 ± 0.67)%, 43.04 ± 37.61, respectively. The recovery time of AA patients was (22.00 ± 9.08)%, (3.46 ± 2.26)%, 10.49 ± 7.80 Compared with the normal control group, the incidence of CD28 in AA patients was significantly higher (P <0.05), CTLA-4 significantly decreased (P = <0.01), and the ratio of CD28 + / CTLA-4 + (P <0.05), while the recovery of the above values compared with the normal control group, the difference was not statistically significant (P> 0.05). ② The ratio of Th1 / Th2 in Th1 and Th2 cells in normal control group was (4.21 ± 2.11)%, (1.99 ± 1.27)%, 2.46 ± 1.28, (11.13 ± 4.96)% and (2.46 ± 1.65)% , 5.20 ± 1.98 respectively, and recovery time was (5.39 ± 4.29)%, (2.53 ± 2.41)% and 2.87 ± 1.43 respectively. Compared with the normal control group, the Th1 in the onset stage of AA was increased and the Th1 and Th2 balances shifted to Th1 All <0.01), the recovery period compared with the normal control group, the difference was not statistically significant. (3) There was a positive correlation between the ratio of CD28 ~ + / CTLA-4 ~ + and the Th1 / Th2 ratio in AA patients (P <0.05). ANC was negatively correlated with the number of CD3 ~ + CD4 ~ + CD28 ~ + T cells ~ + CD4 ~ + CTLA-4 ~ + T cells was positively correlated (P <0.01). Conclusions ① The expression of costimulatory molecules on the surface of CD4 ~ + T cells in patients with AA is abnormal, CD28 is elevated, CTLA-4 is decreased, and bone marrow T cells in AA patients are in “preactivation” state; ②The ratio of CD28 / CTLA- / Th2 ratio was positive correlation Tip: CD28, CTLA-4 imbalance can cause Th cell pattern shift, Th1-type cells increased. ③ The correlation analysis of ANC, CD28 and CTLA-4 further indicated that CD28 and CTLA-4 are associated with the occurrence and development of AA.