Cord blood dendritic cells prevent the differentiation of naïve T-helper cells towards Th1 irrespective of their subtype

Abstract

Allogeneic cord blood transplantation is associated with a less severe graft-versus-host disease (GVHD). This observation is thought to be due to immaturity of cord blood cell immune capabilities. Dendritic cells (DCs) are the most potent antigen-presenting cells of the immune system capable of initiation and regulation of immune responses. In this investigation, we hypothesized that non-manipulated cord blood dendritic cells (CBDCs) not only differ in their functional maturity from adult peripheral blood DCs (PBDCs) but also differ in their subsets and their preference in promoting Th1 or Th2 immune responses. Non-manipulated fresh DCs were isolated from cord blood (CB) and adult peripheral blood (PB) mononuclear cells as lineage marker negative cells. The differences in expression of costimulatory molecules, the proportion of myeloid and lymphoid DCs subsets, their immunostimulatory characteristics and their influence on promoting the differentiation of naïve T cells towards Th1 or Th2 cells were then investigated in these two populations. Our results showed that freshly isolated CBDCs, similar to cord blood monocyte derived DCs, were poor inducers of IFN-gamma secretion while they increased the induction of IL-4 production by T cells in comparison with PBDCs. CBDCs were also poor stimulators of allogenic T cells in mixed leukocyte reaction compared to adult peripheral blood dendritic cells. They also displayed decreased expression of HLA-DR and CD86 molecules. The ratio of lymphoid DCs (CD11c(-), CD123(+)) to myeloid DCs (CD11c(+), CD123(-)) was significantly higher in CB compared to PB. We conclude that CBDCs preferential priming of naive T cells towards Th2 population, seems to be an intrinsic property independent of their subtype. This property along with their functional immaturity should contribute to outcome of cord blood transplantation.