CD8+ T cells suppress autologous megakaryocyte apoptosis in idiopathic thrombocytopenic purpura

To investigate the effect and mechanism of the CD8⁺ T cells in bone marrow on autologous megakaryocytopoiesis in idiopathic thrombocytopenic purpura (ITP) patients, we prepared bone marrow mononuclear cells (MNCs) from 15 chronic ITP patients and 13 controls. MNCs were cultured in vitro directly (MNC group) or after depleting CD8⁺ T cells (CD8⁺ T-dep group) or adding purified autologous CD8⁺ T cells to CD8⁺ T-dep MNCs (Coculture group) or adding dexamethasone to the coculture (DEX group) all in semi-solid and liquid culture systems. The quantity and quality of megakaryocytes were measured. The megakaryocyte count was increased in the presence of autologous CD8⁺ T cells of patients with chronic ITP, while platelet production was reduced. In addition, lower percentages of polyploidy and apoptotic megakaryocytes, and higher levels of soluble Fas (sFas) in supernatant were observed. Dexamethasone successfully corrected this effect of CD8⁺ T cells on autologous megakaryocytopoiesis. These studies provide evidence that activated CD8⁺ T cells in bone marrow of patients with chronic ITP might suppress megakaryocyte apoptosis, leading to impaired platelet production. Megakaryocyte apoptosis would be a novel target for the management of ITP.