Studies of human cord blood dendritic cells: evidence for functional immaturity

Abstract

We have isolated low-density, nonadherent, nonphagocytic, HLA-DR+ve cells with the morphology of dendritic cells (DCs) from the cord blood of full-term newborn infants. Relative to adult DCs, cord blood DCs were poor stimulators of the mixed leukocyte reaction when either adult or cord blood mononuclear cells (MNCs) or T lymphocytes were used as responder cells. In contrast, cord blood T cells and MNCs responded normally to allogeneic adult DCs. Cord blood DCs performed poorly as accessory cells for T-lymphocyte mitogenic responses at suboptimal concentrations of concanavalin A (Con A) and phytohemagglutinin A or at optimal concentrations of mitogen and low numbers of DCs. Addition of recombinant interleukin-2 (rIL-2) or recombinant interferon-gamma (rIFN-gamma) to cord blood DC-T-cell cultures containing a suboptimal concentration of Con A potentiated the proliferative response. In contrast, rIL-2 and rIFN-gamma exerted little effect on the proliferative response of adult T cells cultured with Con A and DCs. Flow cytometric studies showed that levels of intercellular adhesion molecule-1 (ICAM-1; CD54) and major histocompatibility complex (MHC) class I HLA-ABC and class II HLA-DR antigens on cord blood DCs were significantly lower than those on adult blood DCs. These findings suggest that the relative inefficiency of cord blood DCs in the activation of T cells may be related to their low cell surface expression of MHC and cell adhesion molecules. The demonstrated impairment of cord blood DC function could be of importance in understanding the immunologic relationship between the fetus and mother and could contribute to the susceptibility of newborns to infection.