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

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)-α 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-α 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.