Increased frequency and suppressive function of CD4+ CD25^high regulatory T-cells in acute myeloid leukemia patients

Abstract

7054 Background: Regulatory CD4+CD25+ T cells (T reg) are critical regulators of immune tolerance. However, the functional role of T reg in human tumor immunity has been less well studied. The frequency of circulating Treg is increased in patients with solid malignancies. We evaluated the frequency, phenotype and suppressive function of T reg in patients with acute myeloid leukemia (AML). Methods: The frequency and phenotype of CD4+ CD25high T cells were investigated in the peripheral blood of fifteen newly diagnosed AML patients prior to any treatment and fifteen healthy donors by multiparameter flow cytometry. The suppressive function of Treg was evaluated using CFSE-labeled fresh autologous CD4+CD25- T cells activated with an anti-CD3 antibody. Results: The percentage of circulating CD4+ CD25high Treg was higher (p <0.001) in the AML patients (5.2 ± 1.3%, range 0.4 −7%) compared to healthy donors (1.1 ± 0.2%, range 0.8–1.5%). T reg expressing Foxp3, CTLA-4, CD45 RO, CCR4 and Fas receptor (CD95) were significantly elevated in the circulation of AML patients, but GITR expression on Treg was low. Suppression mediated by T reg co-incubated with proliferating autologous responders was also significantly higher (p<0.001) in AML than that mediated by control T reg (75 ± 6% vs 12%± 4%). Conclusions: These results indicate that T reg accumulate in the periphery of patients with AML and have vigorous suppressive functions. This high suppressive activity may impair the host anti-tumor responses and promote leukemogenesis. No significant financial relationships to disclose.