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 nonmanipulated 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-c 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.

Activation of cord blood myeloid dendritic cells by Trypanosoma cruzi and parasite-specific antibodies, proliferation of CD8+ T cells, and production of IFN-γ

“…Another interesting result is that T. cruzi-activated cord blood eDCs favored the production of IFN-c over IL-13, whereas in the absence of parasites, cord blood eDCs displayed a type 2 response releasing higher levels of IL-13, as previously described [21,22]. We can reasonably hypothesize that CD8 ?…”

“…Neonatal DCs display defective expression of co-stimulatory molecules [10,[12][13][14][15][16] and a deficient production of the type 1 polarizing cytokines interleukin (IL)-12 and IFN-b [17,18]. They are less effective than adult DCs in stimulating T cell proliferation [19,20] and induce a poor Th1 response [21,22].…”

Direct and indirect antigen presentation lead to deletion of donor-specific T cells after in utero hematopoietic cell transplantation in mice

“…Alternatively, if umbilical cord blood is transplanted, the DCs are immature and Th1 responses may be curtailed. 34 Thus, the relative importance of each pathway must be determined empirically for newer donor cell populations such as embryonic stem cell-derived HSCs or stem cells which do not give rise to APCs.…”

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

“…The final published version may differ from this proof. 11 11 the UCB-derived monocytes was lower than that of APB-derived monocytes (Fig. 1B).…”

“…However, its application is now limited to only children since the absolute number of hematopoietic stem cells in a unit of UCB is too low to be applied to adults [9]. Previous studies have demonstrated that UCB-DCs display a low level of co-stimulatory molecules, low responsiveness to microbial components, and low lymphocyte-activating capacities [10,11]. These tolerogenic properties of UCB-DCs lead to alleviation of immune rejection after the transplantation [12].…”