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慢性特发性血小板减少性紫癜中自体血小板的细胞介导溶解。

Cell-mediated lysis of autologous platelets in chronic idiopathic thrombocytopenic purpura.

作者信息

Zhang Feng, Chu Xiaoxia, Wang Lin, Zhu Yuanyuan, Li Lizhen, Ma Daoxin, Peng Jun, Hou Ming

机构信息

Hematology Oncology Center, Qilu Hospital of Shandong University, Jinan, Shandong, China.

出版信息

Eur J Haematol. 2006 May;76(5):427-31. doi: 10.1111/j.1600-0609.2005.00622.x. Epub 2006 Feb 15.

Abstract

OBJECTIVES

Investigate the contribution and mechanism of cell-mediated cytotoxicity to the pathogenesis of idiopathic thrombocytopenic purpura (ITP).

METHODS

We observed the cytotoxic effect of cytotoxic T-lymphocyte (CTL) (CD8+) and natural killer cells (CD3- CD16+ CD56+) toward chronic ITP patient's autologous platelets, and investigated the expression of Fas ligand (FasL), tumor necrosis factor (TNF)-alpha and TNF-related apoptosis inducing ligand, as well as perforin and granzyme B mRNA in CD8+ cells using flow cytometry and reverse transcriptase-polymerase chain reaction.

RESULTS

We found that platelet lysis was seen only using purified CD8+ T cells as effector cells; expression of FasL and TNF-alpha in CD8+ T cells in ITP group was elevated. Moreover, the mRNA levels of granzyme B and perforin in CD8+ cells of ITP patients were increased.

CONCLUSIONS

Our findings suggest that CTLs are activated in chronic ITP and might be involved in the pathogenesis of this disorder. Apoptosis and perforin/granzyme-mediated cytotoxicity constitute an important pathway through which CTLs destruct autologous platelets. CTLs might be a reasonable target for a therapeutic strategy.

摘要

目的

研究细胞介导的细胞毒性在特发性血小板减少性紫癜(ITP)发病机制中的作用及机制。

方法

我们观察了细胞毒性T淋巴细胞(CTL,CD8 +)和自然杀伤细胞(CD3 - CD16 + CD56 +)对慢性ITP患者自体血小板的细胞毒性作用,并使用流式细胞术和逆转录聚合酶链反应研究了Fas配体(FasL)、肿瘤坏死因子(TNF)-α和TNF相关凋亡诱导配体以及穿孔素和颗粒酶B mRNA在CD8 +细胞中的表达。

结果

我们发现仅使用纯化的CD8 + T细胞作为效应细胞时可见血小板裂解;ITP组CD8 + T细胞中FasL和TNF-α的表达升高。此外,ITP患者CD8 +细胞中颗粒酶B和穿孔素的mRNA水平增加。

结论

我们的研究结果表明,CTL在慢性ITP中被激活,可能参与了该疾病的发病机制。凋亡和穿孔素/颗粒酶介导的细胞毒性构成了CTL破坏自体血小板的重要途径。CTL可能是治疗策略的合理靶点。

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