title: Monocyte derived dendritic cells have reduced expression of co-stimulatory molecules but are able to stimulate autologous T-cells in patients with MDS.
abstract: BACKGROUND
  Research has implied that the immune system plays a role in the pathogenesis of MDS and that T-cells are reacting to tumour antigen present on the surface of the malignant cells. This could imply that the immune system could be utilized to generate immune based therapy. The aim of this pilot study was to examine the feasibility of studying this further by analysing the interaction of dendritic cells with T-cells in a small cohort of MDS patients.
  
  
  METHODS
  Dendritic cells were generated in 6 MDS patients and 9 controls by culturing monocytes with GM-CSF and IL-4. After activation with LPS and TNFα, the dendritic cells were analyzed for expression of co-stimulatory and activation antigens. Thereafter, they were co-cultured with T-cells and the T-cell response was examined by measuring the % change in expression of the activation antigen CD69.
  
  
  RESULTS
  MDS MoDC had reduced expression of HLA-DR (p=0.006), CD11c (p=0.0004), CD80 (p=0.03) and CD86 (p=0.003), while resting T-cells from MDS patients had higher expression of the activation antigen CD69 on all subsets. The % change in CD69 expression increased significantly for both the control and MDS T-cells after co-culture with allogeneic dendritic cells, however this change was lower in the MDS group. Despite the increased CD69 expression prior to culture, MDS MoDC significantly up-regulated CD69 expression on autologous T-cells to values that were statistically higher than control cells.
  
  
  CONCLUSIONS
  This initial study suggests that the T-cells in MDS are able to respond to dendritic cells and are therefore probably not part of the malignant clone. It further implies that the dendritic cell population could be capable of presenting antigen and initiating an immune response and therefore further study is both feasible and warranted.
authors.affiliation: Department of Biomedical Sciences, Faculty of Health and Wellness Sciences, Cape Peninsula University of Technology, South Africa.
authors.forename: Glenda M
authors.initials: GM
authors.lastname: Davison
authors.forename: Nicolas
authors.initials: N
authors.lastname: Novitzky
authors.forename: Rygana
authors.initials: R
authors.lastname: Abdulla
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D002478:Cells, Cultured; D018920:Coculture Techniques; D015331:Cohort Studies; D003713:Dendritic Cells / Q000166:cytology*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007167:Immunotherapy; D015847:Interleukin-4 / Q000494:pharmacology; D037181:Lectins, C-Type / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects; D009190:Myelodysplastic Syndromes / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D010865:Pilot Projects; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D015847:Interleukin-4; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D000099192:CD69 Antigens