Extracorporeal photopheresis affects co-stimulatory molecule expression and interleukin-10 production by dendritic cells in graft-versus-host disease patients

Graft-versus-host disease (GVHD) is a major complication of allogeneic bone marrow transplantation. Extracorporeal photochemotherapy (ECP) has been introduced as an alternative treatment for GVHD refractory to conventional immunosuppressive treatment, although its mechanism of action is not yet clear. We investigated, in seven GVHD patients, the effects of ECP on dendritic cell maturation and cytokine production in an in vitro model that could mimic the potential in vivo effect of reinfusion of ECP-treated peripheral blood mononuclear cells. The model was based on co-culture of ECP-treated lymphocytes with monocyte-derived dendritic cells (DCs) of the same patient. We found that the co-culture of ECP-treated lymphocytes with immature DCs reduced CD54, CD40 and CD86 mean fluorescence intensity (MFI) significantly after lipopolysaccharide (LPS) stimulation, without affecting human leucocyte antigen D-related and CD80 MFI. In the same co-culture model, DCs produced increased amounts of interleukin (IL)-10 when co-cultured with ECP-treated lymphocytes and stimulated with LPS, while IL-12 and tumour necrosis factor-alpha production were not affected. These results suggest that reinfusion of large numbers of autologous apoptotic lymphocytes is significant for the therapeutic outcome of ECP through down-regulation of co-stimulatory molecules on DCs, inducing non-fully mature DCs with a low signal 2 and up-regulation of IL-10, which is an immunosuppressive cytokine.