Changes Of Regulatory T Cells And Their Associated Cytokines In Patients With Chronic Myeloid Leukemia

Objective To investigate the changes in the proportion of regulatory T(Treg) cells and in the levels of cytokines secreted by these cells in the peripheral blood in the patients with chronic myeloid leukemia(CML). Methods The enrolled subjects consisted of 30 CML patients who were newly diagnosed, 20 CML patients who were under the effective treatment of tyrosine kinase inhibitors(BCR-ABL 210 transcript ratio was below 10%) and 20 healthy donors whose age and sex were matched. Flow cytometry was used to detect CD4+CD25+CD127low/- Treg cells and CD4+ T cells. The enzyme linked immunosorbent assay was used to determine the plasma concentrations of interleukin-10, transforming growth factor-β1(TGF-β1) and interleukin-35. Results The proportions of CD4+CD25+CD127low/- Treg cells in CD4+ T cells were similar among the three groups(F = 2.983,P > 0.05). With regard tothe three kinds of Treg-associated cytokines, there were no significant differences in the plasma concentrations of interleukin-10 among the three groups(H = 4.273,P > 0.05). However, the plasma concentrations of interleukin-10 in the chronic phase ofthe newly diagnosed patients positively correlated with white blood cell counts(r = 0.476, P = 0.016) and spleen size(r = 0.511, P = 0.009). Compared with the treatment group and the control group, the plasma concentrations of TGF-β1 and interleukin-35 in the newly diagnosed patients significantly increased(Ps< 0.001), with no significant difference between the treatment group and the control group. The plasma concentrations of TGF-β1 positively correlated with platelet counts(r = 0.399, P = 0.048) and Sokal scores(r = 0.417, P = 0.038) in the chronic phase in the newly diagnosed patients. There was a positive correlation between the plasma concentrations of interleukin-35 and white blood cell counts in the chronic phase in the newly diagnosed patients(r = 0.403, P = 0.046).However, the plasma concentrations of interleukin-10, TGF-β1 and interleukin-35 had no correlations with each other in the chronic phase in the newly diagnosed patients(Ps >0.05). Furthermore, in the chronic phase of the newly diagnosed patients, the proportion of CD4+CD25+CD127low/- Treg cells in CD4+ T cells had no correlations with the plasma concentrations of all the three kinds of cytokines(Ps > 0.05). Conclusion The proportion of Treg cells did not significantly change in thenewly diagnosedpatients and has no correlations with the progression of CML.The plasma concentrations of TGF-β1and interleukin-35 indeed significantly enhanced, suggesting the dysfunction of immune systemin thenewly diagnosedpatients and the progression of disease might interact as both cause and effect. Effective treatment of tyrosine kinase inhibitors could down-regulate the plasma levels of these cytokines to baseline, suggesting that monitoring these cytokinesmightevaluatethe efficacy of therapy.