Identification of both myeloid CD11c⁺ and lymphoid CD11c⁻ dendritic cell subsets in cord blood

Abstract

Summary. Dendritic cells (DCs) are the most potent antigenpresenting cells described to date. In human peripheral blood, both myeloid and lymphoid subsets of DCs have been identified. In contrast, cord blood (CB) DCs have recently been described as being exclusively of the immature CD11c 2 lymphoid DC subset. Using an alternative method of enrichment, based on a negative selection system, both lymphoid (HLA-DR 1 CD123 111 CD11c 2 CD33 2 ) and myeloid (HLA-DR 11 CD123 1 CD11c 1 CD33 1 ) DCs were identified in CB. Although the majority of CB DCs showed a lymphoid phenotype, a significant number of CD11c 1 myeloid DCs (25´6%^14´5%, n 13) were also present.Other markers, such as CD80 and CD83, were negative in both subsets. Analyses of the allostimulatory capacity of both subsets showed that freshly isolated CB lymphoid DCs failed to induce a potent allostimulation of naive CB T cells. These features are therefore consistent with previous work reporting an immature phenotype for lymphoid DCs in adult blood. The significance of the inverted CD11c 1 /CD11c 2 ratio observed in CB DCs (1:3) with respect to adult blood DCs (3:1) remains to be explained.

Defective antigen-presenting cell function in human neonates

“…In general, an increased number and proportion of pDCs was reported in CB compared to adult peripheral blood. Widely-different pDC:mDC ratios in CB have been reported by different investigators, ranging from 1:1 to 3:1 [39][40][41][42][43]. Nevertheless, since the usual pDC:mDC ratio in adults is 1:2, a consensus towards increased pDC:mDC ratio in CB is emerging from these studies.…”

“…The ability of CB-DCs to capture antigenic protein is also altered, suggesting that those cells may in fact not function properly as APCs [27]. However, this hypothesis is challenged by the fact that unfractionated CB-DCs induce strong allogeneic responses [39], suggesting a complex picture in terms of the functionality of neonatal DCs. In that regard, data obtained in babies who have been exposed in utero to viruses bring some important information.…”

“…When the capacity of CB-DCs to stimulate allogeneic CB T cells was analyzed, weak proliferation was observed in pDC-stimulated cultures compared to total CB-DC-stimulated ones [39], which was linked to an increased proportion of apoptotic T cells in the former cultures. Mechanisms underlying such data have not been elucidated and could involve either a direct apoptotic signal given by CB-pDCs or a failure in the induction of rescuing signals.…”

“…CB-DCs appear to be immature, as they exhibit low or no basal expression of CD40, CD80 or CD86 [27,39]. In the latter study, DCs were identified as Lin − /HLA-DR + , and differential evaluation of costimulatory molecules on pDCs vs mDCs was not done.…”

Generation of functional natural killer and dendritic cells in a human stromal-based serum-free culture system designed for cord blood expansion

“…Some of the major advantages of this culture system include the use of pre-established human allogeneic stromal layers, thus overcoming the limitations of using xenogeneic and/or transformed and immortalized human stromal cell lines, this culture system's serum-free conditions, and its ability to expand CB cells along the myeloid pathway, while simultaneously generating a population expressing a marker of early lymphopoiesis, CD7 + . Since several different investigators had reported the ability to generate NK, B, DCs and T cells [10,[16][17][18][19][20][21][22]] from a CD7 + CD34 + cell population from fresh CB and BM, in the present studies, we examined whether the CD7 + CD34negative population obtained after CB expansion over MSC layers, in serum-free medium, also had lymphocytic differentiative potential. Specifically, we investigated the ability of the CD7+ population generated in our culture system to give rise to two of the major constituents of the immune system, mature NK cells and dendritic cells (DCs) that could ultimately be used in cellular immunotherapy.…”