Extracorporeal photopheresis in cutaneous T-cell lymphoma and graft-versus-host disease induces both immediate and progressive apoptotic processes

BACKGROUND: Extracorporeal photopheresis (ECP) therapy is used in the treatment of many T-cell-mediated conditions including cutaneous T-cell lymphoma and graft-versus-host disease and involves the reinfusion of a patient's own white cells following exposure to 8-methoxypsoralen and ultraviolet A. ECP has been demonstrated to induce significant levels of apoptosis in treated lymphocytes. Previous work has highlighted the importance of mitochondria and the caspase cascade in the regulation and execution of apoptosis and, more recently, a functional role for CD10 has been proposed for apoptotic lymphoid cells in vivo. OBJECTIVES: To determine the effect of ECP on phosphatidylserine (PS) exposure, mitochondrial function, caspase activation and CD10 expression of treated lymphocytes. METHODS: Lymphocytes were tested pre-ECP and at several stages post-ECP for changes to PS, mitochondrial transmembrane potential (DeltaPsim), activated caspases and CD10 expression. RESULTS: Early apoptosis induced a disruption in DeltaPsim, while caspase activation was not observed until 24 h post-ECP. CD10 expression was very weak and "late" in the apoptotic process. CONCLUSIONS: The early induction of apoptosis by ECP involves mitochondrial dysfunction, while later apoptosis is associated with the activation of caspases. CD10 expression was very weak and "late", preceded by a strong PS exposure. These apoptotic processes, in vivo, would induce the immediate and progressive phagocytosis of the majority of ECP-treated lymphocytes within 48 h.