Defective tumor necrosis factor alpha-induced maturation of monocyte-derived dendritic cells in patients with myelodysplastic syndromes.
Myelodysplastic syndromes (MDS) are clonal stem cell disorders, characterized by ineffective and dysplastic hematopoiesis. MDS patients have a defective immune response manifested by increased susceptibility to bacterial infections, autoimmune phenomena, and high incidence of lymphoid malignancies. Presently, we investigated the phenotype and function of monocyte-derived dendritic cells (MoDC) in 23 MDS patients and 15 controls at different stages of differentiation using the maturation stimuli tumor necrosis factor-alpha (TNF-alpha) and LPS. Monocytes from MDS patients showed low potential to differentiate into dendritic cells (DC), as determined by low cell yield and CD1a expression. MDS-MoDCs exhibited low expression of mannose receptor and reduced endocytic capacity. MDS-MoDCs showed a diminished response to TNF-alpha with low CD83, CD80, and CD54 expression and allostimulatory capacity. In patients with 5q syndrome, monocytes and MoDCs were positive for the 5q deletion, suggesting their origin from the malignant clone. Our data indicate that MoDCs in MDS display quantitative and functional abnormalities that may contribute to the defective immune response of these patients.
Micheva
Ilina
I
Hematology Division, Department of Internal Medicine, Medical School and University Hospital, University of Patras, Patras, Greece. idm@med.upatras.gr
Thanopoulou
Eleni
E
Michalopoulou
Sotiria
S
Karakantza
Marina
M
Kouraklis-Symeonidis
Alexandra
A
Mouzaki
Athanasia
A
Zoumbos
Nicholas
N
D000368:Aged; D000369:Aged, 80 and over; D000941:Antigens / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D004705:Endocytosis; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism; D008297:Male; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000378:metabolism; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D009190:Myelodysplastic Syndromes / Q000473:pathology*; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000941:Antigens; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D014409:Tumor Necrosis Factor-alpha