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Keywords:

  • myelodysplastic syndrome;
  • Foxp3;
  • regulatory T cells;
  • CD8/Foxp3 ratio;
  • Th1/Th2 ratio

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).

Patients and 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 × 109/L; 95% CI, 0.02–0.10 × 109/L) and RAEB group (0.06 × 109/L; 95% CI, 0.02–0.10 × 109/L) were significantly higher than that of the control group (0.03 × 109/L; 95% CI, 0.02–0.03 × 109/L) (P < 0.05). However, in the RCMD group, there was no significant difference in the mean absolute number of Tregs (0.03 × 109/L; 95% CI, 0.02–0.04 × 109/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.