Phenotypic and functional characteristics of monocyte-derived dendritic cells from patients with myelodysplastic syndromes

We have compared the phenotypic and functional characteristics of dendritic cells (DC) generated in vitro from the peripheral blood mononuclear fracti on of myelodysplastic syndrome (MDS) patients (four refractory anaemia, fou r refractory anaemia with excess of blasts) with DCs generated in a similar way from eight healthy donors. After 10 d of culture in the presence of GM -CSF and IL-4, reduced numbers and percentages of DCs were obtained in MDS subjects, MDS DCs exhibited significantly lower expression of CD1a, CD54, C D80 and MHC class II molecules. Their ability to stimulate T lymphocytes in an allogeneic mixed leucocyte reaction was reduced in comparison to normal subjects. Furthermore, MDS DCs also showed a reduced receptor-mediated end ocytosis as demonstrated by FITC-dextran uptake. Simultaneous fluorescence in situ hybridization (FISH) and immunophenotypic analysis demonstrated tha t MDS DCs have the same cytogenetic abnormality of the malignant clone. Tak en together these findings indicate that, in MDS, DCs are part of the malig nant clone and exhibit a deficient antigen uptake and presentation.