Maturation state of dendritic cells during the extracorporeal photopheresis and its relevance for the treatment of chronic graft‐versus‐host disease

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Abstract
Chronic graft-versus-host disease (cGVHD) represents a major cause of morbidity and mortality after allogeneic bone marrow transplantation (BMT). Extracorporeal photochemotherapy (ECP), a technique used in the treatment of cutaneous T-cell lymphoma, has also shown clinical efficacy in the treatment of refractory cGVHD. In this study, the dynamics of dendritic cell (DC) activation were investigated during the process of photopheresis in patients treated for refractory cGVHD. It is reported that myeloid DCs can be isolated from the photopheretic products before retransfusion to the patient. It is shown that DCs in ECP product are in the immature state with respect to the phenotypic and functional characteristics. In contrast to the in vitro-generated monocyte-derived DCs and DCs not treated by 8-methoxypsoralen and UVA, they produce significant amounts of interleukin-10 (IL-10). They efficiently capture apoptotic lymphocytes and do not induce proliferation of T lymphocytes. They preserve the capacity to be activated by polyriboinosinic polyribocytidylic acid and lipopolysaccharide, however. ECP also induces rapid and massive apoptosis of alloreactive lymphocytes. A model of the potential implication of IL-10-producing DCs in the down regulation of harmful alloreactive immune reaction is presented. It is believed that this study provides a novel insight into the mechanisms of action of ECP in the control of cGVHD.