Zhang Feng, Chu Xiaoxia, Wang Lin, Zhu Yuanyuan, Li Lizhen, Ma Daoxin, Peng Jun, Hou Ming
Hematology Oncology Center, Qilu Hospital of Shandong University, Jinan, Shandong, China.
Eur J Haematol. 2006 May;76(5):427-31. doi: 10.1111/j.1600-0609.2005.00622.x. Epub 2006 Feb 15.
Investigate the contribution and mechanism of cell-mediated cytotoxicity to the pathogenesis of idiopathic thrombocytopenic purpura (ITP).
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.
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.
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.
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。
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。
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。
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。
