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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Encabo
Araceli
A
University General Hospital Foundation, Valencia, Spain.
Solves
Pilar
P
Carbonell-Uberos
Francisco
F
Miñana
Maria Dolores
MD
D000328:Adult; D017252:CD3 Complex / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D036101:Cord Blood Stem Cell Transplantation; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology*; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000276:immunology / Q000517:prevention & control; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D016130:Immunophenotyping; D015994:Incidence; D007371:Interferon-gamma / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D016131:Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D017252:CD3 Complex; D015704:CD4 Antigens; D053645:Interleukin-2 Receptor alpha Subunit; D018950:Lipopolysaccharide Receptors; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma