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Summary:Cord blood (CB) transplantations are associated with low graft-versus-host disease (GVHD). The pathophysiology of GVHD involves interaction and activation of different cell types, as lymphocytes and monocytes, and results in a cascade of cytokine production. After antigen or mitogen stimulation, CB monocytes release lower levels of cytokines than adult blood (AB) monocytes. In this study, the detection of intracellular IL-1␤ and TNF-␣ produced by monocytes was evaluated in response to tuberculin PPD to investigate whether the reduced capacity of CB monocytes to secrete cytokines could be related to an impaired functional activity and to a particular phenotypic profile. Results showed that the percentage of CD64 + monocytes producing intracellular IL-1␤ and TNF-␣ was significantly lower in CB and that the phenotypic profile of CB monocytes producing these cytokine (CD64 + CD14 + ) was different to that of AB monocytes (CD64 + CD14 + , CD64 + CD33 + and CD64 + CD45RO + ). These results suggest that the lower capacity of CB monocyte populations to produce IL-1␤ and TNF-␣ might be due to a functional immaturity of CB monocytes at the cellular level as reflected by the different phenotypic profile of CB monocytes. Bone Marrow Transplantation (2001) 27, 1081-1086. Keywords: cord blood monocytes; intracellular cytokine; GVHD; bone marrow transplantation Clinical observations of umbilical CB transplantation show a reduced incidence of GVHD compared to allogeneic bone marrow transplantation (BMT). 1,2 GVHD is an immune reaction which results from a complex network of interactive cells producing or responding to a variety of cytokines and target structures. Its development involves activation of donor-derived T cells recognizing alloantigens presented by host-or donor-derived antigen presenting cells (APCs). However, the clinical manifestations result largely from cytokine dysregulation. 3,4 Comparison of the ability of CB and AB cells to produce cytokines has been analyzed by several groups and showed differences in their functional behavior. 5-9 Our previous study showed that after recombinant IFN-␥ stimulation, CB monocytes released lower levels of IL-1␤ and TNF-␣ than AB monocytes. 10 These cytokines have multiple immunological and inflammatory functions and are known to play a crucial role in the pathogenesis of GVHD. 11,12 Since cytokine production is an indication of cell function, the aim of this work was to determine intracellular production of cytokines in order to investigate whether the reduced capacity of CB monocytes to secrete IL-1␤ and TNF-␣ could be related to an impaired functional activity and to a particular phenotypic profile of CB monocytes. IL-1␤ and TNF-␣ production by PPD-stimulated cord and adult blood monocytes was assessed at the single cell level by flow cytometry. Materials and methods Collection of CB and AB samplesCord blood samples (n = 10) were obtained from normal full-term deliveries and collected through the umbilical vein, after delivery and before the expulsion of the placent...

Umbilical cord blood (CB) transplantations are associated with a lower risk of severe graft-versus-host disease (GVHD) compared to BMT. GVHD is an immune reaction that involves interaction between cell surface molecules resulting in cell activation and release of many cytokines. Monocytes are known to be an important source of cell adhesion (CAM) and co-stimulatory molecules which play a crucial role in the efficient activation of T and B cells. We analyzed the phenotype of CB monocytes in the presence or absence of an inflammatory signal (rIFN-gamma) and compared them to adult blood (AB); the expression of HLA-DR and 17 different markers (CD11a, CD11b, CD11c, CD18, CD29, CD40, CD44, CD49a, CD49d, CD49e, CD49f, CD54, CD58, CD62L, CD80, CD86 and CD102) was measured by flow cytometry. Statistical analysis showed that, compared to AB, CB monocytes did not express CD11b, CD11c, CD49d and after stimulation with rIFNgamma, they lost the expression of CD58 and CD102, whereas CD80 and CD86 expression was induced. The analysis of fluorescence intensity (MFI) revealed that CB monocytes expressed some CAM (CD29, CD54, CD102) with a lower intensity than AB monocytes except CD44. In conclusion, absence and reduced expression of some markers argue for a different phenotypic profile of CB monocytes compared to AB monocytes, which might partly contribute to their impaired immune response and to the low incidence of GVHD observed after CB transplantations. However, CB monocytes expressed CD80 and CD86 co-stimulatory molecules, but this expression did not prove a normal co-stimulatory function.

Umbilical cord blood (CB) transplantations are associated with a lower risk of severe graft‐versus‐host disease (GVHD) compared to BMT. GVHD is an immune reaction that involves interaction between cell surface molecules resulting in cell activation and release of many cytokines. Monocytes are known to be an important source of cell adhesion (CAM) and co‐stimulatory molecules which play a crucial role in the efficient activation of T and B cells. We analyzed the phenotype of CB monocytes in the presence or absence of an inflammatory signal (rIFN‐γ) and compared them to adult blood (AB); the expression of HLA‐DR and 17 different markers (CD11a, CD11b, CD11c, CD18, CD29, CD40, CD44, CD49a, CD49d, CD49e, CD49f, CD54, CD58, CD62L, CD80, CD86 and CD102) was measured by flow cytometry. Statistical analysis showed that, compared to AB, CB monocytes did not express CD11b, CD11c, CD49d and after stimulation with rIFNγ, they lost the expression of CD58 and CD102, whereas CD80 and CD86 expression was induced. The analysis of fluorescence intensity (MFI) revealed that CB monocytes expressed some CAM (CD29, CD54, CD102) with a lower intensity than AB monocytes except CD44. In conclusion, absence and reduced expression of some markers argue for a different phenotypic profile of CB monocytes compared to AB monocytes, which might partly contribute to their impaired immune response and to the low incidence of GVHD observed after CB transplantations. However, CB monocytes expressed CD80 and CD86 co‐stimulatory molecules, but this expression did not prove a normal co‐stimulatory function.