Dendritic Cells Differentiated from Human Umbilical Cord Blood-Derived Monocytes Exhibit Tolerogenic Characteristics.

Abstract

Human umbilical cord blood (UCB) is rich in diverse hematopoietic stem cells that are competent to differentiate into various cell types with immunological compatibility at transplantation. Thus, UCB is a potential source for the preparation of dendritic cells (DCs) to be used for cell therapy against inflammatory disorders or cancers. However, the immunological properties of UCB-derived DCs are not fully characterized. In this study, we investigated the phenotypes and functions of UCB monocyte-derived DCs (UCB-DCs) in comparison with those of adult peripheral blood (APB) monocyte-derived DCs (APB-DCs). UCB-DCs contained less CD1a(+) DCs, which is known as immunostimulatory DCs, than APB-DCs. UCB-DCs exhibited lower expression of CD80, MHC proteins, and DC-SIGN, but higher endocytic activity, than APB-DCs. Lipopolysaccharide stimulation of UCB-DCs minimally augmented the expression of maturation markers and production of interleukin (IL)-12 and tumor necrosis factor (TNF)-α, but potently expressed IL-10. When UCB-DCs were cocultured with CD14(+) cell-depleted allogeneic peripheral blood mononuclear cells, they weakly induced the proliferation, surface expression of activation markers, and interferon (IFN)-γ production of T lymphocytes compared with APB-DCs. UCB possessed higher levels of prostaglandin E2 (PGE2) than APB, which might be responsible for tolerogenic phenotypes and functions of UCB-DCs. Indeed, APB-DCs prepared in the presence of PGE2 exhibited CD1a(-)CD14(+) phenotypes with tolerogenic properties, including weak maturation, impaired IL-12 production, and negligible T lymphocyte activation as UCB-DCs did. Taken together, we suggest that UCB-DCs have tolerogenic properties, which might be due to PGE2 highly sustained in UCB.