The functional immaturity of dendritic cells can be relevant to increased tolerance associated with cord blood transplantation

Abstract

Cord blood (CB) transplants have a significantly lower incidence of graft-versus-host disease (GVHD) compared to marrow or peripheral blood transplants. Because antigen-presenting cells and regulatory T cells (Treg) are involved in transplant tolerance, this study was aimed at analyzing the distribution of dendritic cells (DCs) and CD14+ monocyte-specific subsets in CB and adult peripheral blood (APB) and comparing the ability of DCs from these two blood sources to induce CD4+ Treg. Myeloid DCs (mDCs), plasmacytoid DCs, the CD14+ cell subsets CD14+CD16+ and CD14+CD209+, and CD4+ T cells were analyzed by fluorescence-activated cell sorting (FACS) in whole blood. To evaluate the functionality of DCs, isolated CD3+ T cells from an adult donor were cultured with allogenic DC-enriched fraction from CB or APB, and CD4+ Treg generation was determined by FACS. Additionally, tumor necrosis factor (TNF)-alpha and interferon (IFN)-alpha release by DCs was measured. CB had a lesser frequency of DCs and specific CD14+ monocyte subsets than APB. After stimulation, monocytes from CB secreted less TNF-alpha than those from APB. Moreover, DCs from CB exhibited a more immature phenotype and had a decreased capacity to release TNF-alpha and IFN-alpha than those derived from APB, but on the contrary, they were efficient inducers of CD4+ T cells with a phenotype of Treg. The tolerogenic immunophenotype and diminished functionality of CB DCs can be important to create a microenvironment where Treg develop, that in turn may be relevant to observed lower incidence of chronic GVHD after CB transplantation.