免疫相关性全血细胞减少症患者骨髓Th细胞比例及功能变化

Subsets and function changes of Th cells in bone marrow of patients with immune-related pancytopenia

目的探讨免疫相关性全血细胞减少症(IRP)患者骨髓中辅助性T淋巴细胞(Th)亚群数量、功能改变及在发病中的作用。方法用流式细胞术同期对照研究16例正常对照组、15例初诊IRP组、24例再生障碍性贫血(AA)组、14例骨髓增生异常综合征(MDS)组骨髓Th细胞改变情况;RT-PCR方法检测10例正常人、25例初诊IRP患者、9例AA患者、9例MDS患者未经体外刺激的骨髓单个核细胞(BMMNC)中Th1细胞的代表因子IFN-γ、IL-2和Th2细胞的代表因子IL-4、IL-10的基因表达。结果(1)骨髓中Th1细胞、Th2细胞及Th1/Th2比值正常对照组为0·42%、0·24%和1·57;初诊IRP组为0·58%、1·95%和0·31;AA组为4·42%、0·41%和21·22;MDS组为0·44%、0·84%和0·96。IRP组Th1细胞与正常对照组及MDS组无显著差异(P>0·05),显著低于AA组(P<0·01);但IRP组Th2细胞显著高于正常对照组、AA组(P<0·01),与MDS组差异未达统计学意义(P=0·054)。IRP组骨髓中Th2细胞占优势,Th1/Th2比值显著低于正常对照组、MDS组及AA组(P<0·01)。(2)与正常对照组比较,初诊IRP组Th2型细胞因子IL-4、IL-10mRNA表达明显增高(P<0·01),而Th1型细胞因子IFN-γ、IL-2mRNA表达无显著增高(P>0·05);AA组Th1型细胞因子显著增高(P<0·01),而Th2型无区别;MDS组未见细胞因子表达增高。结论IRP患者骨髓Th2细胞亚群增多,Th细胞平衡向Th2偏移,且Th2型细胞因子表达增高,细胞功能亢进,可能是IRP免疫发病环节之一,也表明IRP是一种不同于AA和MDS的全血细胞减少症。

Objective To explore the subsets and function of T helper（Th） cells in bone marrow of the patients with immune-related pancytopenia（IRP）. Methods By FACS,Thl and Th2 cells in bone marrow were measured from normal control, IRP patients, aplastic anemia（AA） patients, myelodysplastic syndrome（MDS） patients. The mRNA expressions of IL-4, IL-10, IFN-γ and IL-2 genes in unstimulated bone marrow mononuclear cells （BMMNC） from the normal controls and the patients were measured by RT-PCR. Results The percentages of Th1 cells,Th2 cells and the ratio of Th1/Th2 in bone marrow were 0. 42%,0. 24% and 1.57 in the normal controls,0. 58%,1.95% and 0. 31 in group IRP,4.42%,0. 41% and 21.22 in group AA,0. 44%,0. 84% and 0. 96 in group MDS, respectively. The percentage of Thl cells in untreated patients with IRP was not markedly different from that in the normal controls and MDS（P〉0. 05）, but lower significantly than that in group AA （P〈0. 01）. The percentage of Th2 cells in patients with IRP was significantly higher than that in the normal controls and AA（P〈0. 01）,although was not significantly different from that in group MDS （P〉0. 05）. The balance of Th1/Th2 shifted to Th2 more significantly in LRP patients（P〈0. 01） than that in the normal controls and MDS, while it shifted to Thl in AA patients markedly（P〈0. 01）. Compared to that of normal controls, the mRNA expressions of IL-4 and IL-10 in Th2 cells of the untreated IRP patients,and cytokines of Thl type-IFN-γ and IL-2 in the AA increased significantly, respectively（P〈0. 01） ,and there were no significant changes in MDS patients. Conclusion The percentage of Th2 cells increases in the patients with IRP,and the balance of Th1/Th2 shifts to Th2. And the expression of Th2 type cytokines is more frequent in IRP. The imbalance of subtypes of Th lyrnphocytes and hyperfunction of Th2 lymphocytes may play an important role in the pathogenic mechanism of IRP leading to more B lymphocytes and producing autoantibodies consequently. The results suggest that IRP is a kind of disorder different from AA and MDS.