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)-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.