骨髓增生异常综合征患者骨髓CD4^+T细胞共刺激分子CD28/CTLA-4的变化

Research of CD28/CTLA-4 Costimutatory Molecules Expression on CD4^+ T Cells in Patients with MDS

目的通过检测骨髓增生异常综合征(MDS)患者CD3+CD4+T细胞表面CD28+和CTLA-4+分子水平,探讨两者在MDS发病机制中的作用。方法用流式细胞技术检测38例初治MDS患者和11例正常对照组外周血CD3+CD4+T细胞表面CD28+和CTLA-4+表达率。结果(1)MDS组CD3+CD4+CD28+表达率为(79.82±8.99)%[难治性贫血(RA)(78.65±10.4)%、伴原始细胞增多性难治性贫血(RAEB)/转变中的原始细胞增多性难治性贫血(RAEB-t)(80.10±7.28%)],低于正常对照组的(89.56±3.06)%,差异有高度统计学意义(P﹤0.01);(2)MDS组CD3+CD4+CTLA-4+表达率为(2.14±1.25)%[RA(1.51±0.80)%、RAEB/RAEB-t为(2.65±1.33)%],显著高于正常组的(0.11±0.12)%,差异有高度统计学意义(P﹤0.01);随MDS疾病的进展,RAEB/RAEB-t组CD3+CD4+CTLA-4+的表达率与RA组比较,差异有统计学意义(P<0.05);(3)CTLA-4/CD28免疫应答中相互拮抗的共刺激分子对比值在MDS-RA组中为2.14±0.97,RAEB/RAEB-t组为3.58±1.55,高于正常对照组的0.11±0.11,差异有高度统计学意义(P﹤0.01);并且RA组和RAEB/RAEB-t组之间的差异亦有高度统计学意义(P﹤0.01)。结论(1)MDS患者骨髓的CD3+CD4+T细胞表面的共刺激分子表达异常,CD28下调,CTLA-4上调,T细胞处于抑制状态;(2)随着MDS骨髓中原始细胞的增多,CD28/CTLA-4比值增高,进一步说明CD28/CTLA-4异常与MDS疾病的发生及进展相关。

Objective To detect the expression levels of CD28^＋ and CTLA-4^＋ on CD4^＋ T cells in myelodysplastic syndrome （MDS） patients, and discuss the possible roles of the two costimulatory molecules in MDS mechanism. Methods The levels of CD28^＋ and CTLA-4^＋ on CD3^＋CD4^＋F cells in 38 newly diagnosed MDS patients and the 11 normal controls were detected by flow cytometry. Results （1）Expression of CD3^＋CD4^＋CD28^＋ in MDS patients was （79.82±8.99）% [refractory anemia（RA）（78.65± 10.4）%, RA with excess blasts（RAEB）/RAEB in fransformation（RAEB-t） （80.10±7.28）%], lower than that in the normal controls（89.56±3.06）%（P 〈 0.01 ）.（2）The expression of CD3^＋CD4^＋CTLA-4^＋ in MDS patients was（2.14±1.25）% [RA（1.51±0.80）%, RAEB/RAEB-t（2.65±1.33）%], which was higher than that in the controls （0.11±0.12）% （t=8.66,P 〈 0.01 ）; and along with the progress of disease, the difference between RA and RAEB/RAEB-t was significant （P〈0.05）. （3） The ratio of CTLA-4/CD28 in MDS-RA and RAEB/ RAEB-t was 2.14±0.97 and 3.58±1.55 respectively, higher than that in the controls（0.11±0.11） obviously（P 〈 0.01 ）; and also the difference was significant between RA and RAEB/RAEB-t（P 〈 0.01）. Conclusion （1）Abnormality expression of costimulatory molecules is found on CD3^＋CD4^＋T cells in bone marrow of MDS patients： CD28 increased and CTLA-4 decreased , indicating T cells is in inhibitory state. （2）Along with the progression of MDS, CD28/CTLA-4 changes obviously, which indicate further they correlate with MDS onset and progression.