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.
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.
Authors: Li Ma; Elisa Simpson; June Li; Min Xuan; Miao Xu; Laura Baker; Yan Shi; Issaka Yougbaré; Xiaozhong Wang; Guangheng Zhu; Pingguo Chen; Gerald J Prud'homme; Alan H Lazarus; John Freedman; Heyu Ni Journal: Blood Date: 2015-06-02 Impact factor: 22.113