特发性血小板减少性紫癜中的1型和2型T细胞谱
Type 1 and type 2 T-cell profiles in idiopathic thrombocytopenic purpura.
作者信息
Wang Tingting, Zhao Hui, Ren He, Guo Jianhai, Xu Maoqiang, Yang Renchi, Han Zhong Chao
机构信息
State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, PR China.
出版信息
Haematologica. 2005 Jul;90(7):914-23.
BACKGROUND AND OBJECTIVES
Adult idiopathic thrombocytopenic purpura (ITP) is a chronic acquired organ-specific autoimmune hemorrhagic disease characterized by the production of antibodies against antigens on the membranes of platelet, resulting in enhanced Fc-mediated destruction of the platelets by macrophages in the reticuloendothelial system. Dysfunctional cellular immunity is considered important in the pathophysiology of ITP. The aim of this study was to explore the profile of type1 and type2 T cells in chronic ITP patients.
DESIGN AND METHODS
The balance of Th1/Th2 and Tc1/Tc2 was studied by simultaneous analysis of intracellular cytokines of peripheral blood mononuclear cells and splenocytes in short-term cultures activated with PMA/ionomycin as well as mRNA expression of T-bet and GATA-3 in peripheral blood mononuclear cells and splenocytes using real-time polymerase chain reaction.
RESULTS
Patients with active disease but not patients in remission had significant higher Th1/Th2 (p<0.01) and Tc1/Tc2 (p<0.01) ratios in peripheral blood (PB) and significant higher Th1/Th2 ratio in splenocytes (p<0.01) than those in the control group. The Tc1/Tc2 ratio in splenocytes in ITP patients was higher than that in control, but did not reach significant difference (p=0.082). GATA-3 mRNA expression in ITP patients was significantly lower both in PB (p<0.01) and in splenocytes (p<0.01) than in corresponding samples from controls while there was no difference in T-bet expression.
INTERPRETATION AND CONCLUSIONS
Our data indicate that ITP is a T1 cell (Th1 and Tc1) predominant disease although the precise mechanisms await further functional assay. The T-bet/GATA-3 ratio may provide a surrogate marker of T1/T2 cytokine balance. Shifting the cytokine patterns from T1 to T2 might be a potential immunotherapy for ITP.
背景与目的
成人特发性血小板减少性紫癜(ITP)是一种慢性获得性器官特异性自身免疫性出血性疾病,其特征是产生针对血小板膜上抗原的抗体,导致网状内皮系统中巨噬细胞通过Fc介导增强对血小板的破坏。功能失调的细胞免疫在ITP的病理生理学中被认为很重要。本研究的目的是探讨慢性ITP患者中1型和2型T细胞的特征。
设计与方法
通过同时分析经佛波酯/离子霉素激活的短期培养外周血单个核细胞和脾细胞的细胞内细胞因子,以及使用实时聚合酶链反应分析外周血单个核细胞和脾细胞中T-bet和GATA-3的mRNA表达,研究Th1/Th2和Tc1/Tc2的平衡。
结果
活动期患者外周血中Th1/Th2(p<0.01)和Tc1/Tc2(p<0.01)比值显著高于缓解期患者及对照组,脾细胞中Th1/Th2比值显著高于对照组(p<0.01)。ITP患者脾细胞中Tc1/Tc2比值高于对照组,但差异无统计学意义(p=0.082)。ITP患者外周血和脾细胞中GATA-3 mRNA表达均显著低于相应对照组,而T-bet表达无差异。
解读与结论
我们的数据表明,ITP是一种以T1细胞(Th1和Tc1)为主的疾病,尽管确切机制有待进一步功能分析。T-bet/GATA-3比值可能是T1/T2细胞因子平衡的替代标志物。将细胞因子模式从T1转变为T2可能是ITP的一种潜在免疫治疗方法。