title: Clinical significance of regulatory T cells in patients with myelodysplastic syndrome.
abstract: OBJECTIVE
  Foxp3(+) regulatory T cells (Tregs) play a central role in maintaining immune tolerance. Their expansion in malignant diseases leads to the suppression of host anti-tumour responses. In this study, we evaluated the clinical significance of Tregs in patients with myelodysplastic syndrome (MDS).
  
  
  METHODS
  We analysed the number of CD4(+) CD25(+) Foxp3(+) Tregs using three-colour flow cytometry in the peripheral blood of 26 patients with MDS classified according to the World Health Organization classification method into four cases of refractory anaemia and refractory anaemia with ringed sideroblasts (RA/RARS), 15 cases of refractory cytopenia with multilineage dysplasia (RCMD), three cases of refractory anaemia with excess blast-1 (RAEB-1) and four cases of refractory anaemia with excess blast-2 (RAEB-2). Eighteen healthy volunteers were included as the control group.
  
  
  RESULTS
  The mean absolute numbers of Tregs in the RA/RARS group (0.06 x 10(9)/L; 95% CI, 0.02-0.10 x 10(9)/L) and RAEB group (0.06 x 10(9)/L; 95% CI, 0.02-0.10 x 10(9)/L) were significantly higher than that of the control group (0.03 x 10(9)/L; 95% CI, 0.02-0.03 x 10(9)/L) (P < 0.05). However, in the RCMD group, there was no significant difference in the mean absolute number of Tregs (0.03 x 10(9)/L; 95% CI, 0.02-0.04 x 10(9)/L) compared with the control group. Regarding the mean level of the CD8/Foxp3 ratio, there were significant decreases in the RA/RARS group (2.8; 95% CI, 0.7-4.9; P < 0.01), RCMD group (3.4; 95% CI, 2.0-4.4; P < 0.001) and RAEB group (2.1; 95% CI, 1.7-2.5; P < 0.001) compared with the control group (6.1; 95% CI, 5.1-7.0).
  
  
  CONCLUSIONS
  The expansion of natural CD4(+) Tregs may contribute to the suppression of CD8 through the Th1-mediated immune response in MDS. The low CD8/Foxp3 ratio is a characteristic feature in MDS. To determine whether the expansion of CD4(+) Tregs contributes to the progression of MDS subtypes into more aggressive subtypes, more MDS cases and further follow-up are required.
authors.affiliation: Department of Laboratory Sciences, School of Health Sciences, Gunma University, Gunma, Japan.
authors.forename: Wedad
authors.initials: W
authors.lastname: Hamdi
authors.forename: Hatsue
authors.initials: H
authors.lastname: Ogawara
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Handa
authors.forename: Norifumi
authors.initials: N
authors.lastname: Tsukamoto
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Nojima
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Murakami
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000276:immunology* / Q000473:pathology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology*
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit