Aberrant expression of T cell activation markers and upregulation of Tregs in bone marrow and peripheral blood in acute myeloid leukemia patients

T cells’ function and activation and the immunosuppressive effect of regulatory T cells (Tregs) play a pivotal role in the occurrence and progression of acute myeloid leukemia (AML). In this study, we investigate the expression of T cell activation markers and quantity of Tregs in bone marrow (BM) and peripheral blood (PB) from AML patients and further characterized their correlation with BM leukemic blasts. Expression of CD25, CD38, CD69, and HLA-DR on the surfaces of CD4+ and CD8+ T cells and the quantity of Tregs in BM and PB from new diagnosed (ND), relapsed-refractory (RR), complete remission (CR) AML patients were measured via flow cytometry. Compared to normal controls (NC), we found higher proportion of CD4+ CD69+ T cells, CD8+ CD69+ T cells and Tregs in PB. CD8+ CD38+ T cells and CD8+ HLA-DR+ T cells in RR were significantly higher than ND, CR and NC). Tregs were normalized when AML patients achieved CR. Moreover, there was a minor positive correlation between AML blasts and CD8+ CD25+ T cells or Tregs, while AML blasts had a minor negative correlation with CD4+ CD69+ T cells. Abnormal activation markers of T cells and Tregs may be involved in the pathological mechanism of ND and RR AML. Our results indicated that CD8+ CD38+ T cells and CD8+ HLA-DR+ T cells might be RR markers of AML patients. Furthermore, Tregs could be used as clinical indicators to evaluate prognosis for AML patients.调节性T细胞（regulatory T cells, Tregs）的免疫抑制作用及T细胞（T cells）的功能与活化状态，在急性髓系白血病（acute myeloid leukemia, AML）的发生与疾病进展中发挥关键作用。本研究旨在探究急性髓系白血病患者骨髓（bone marrow, BM）与外周血（peripheral blood, PB）中T细胞活化标志物的表达水平及调节性T细胞的数量，并进一步分析其与骨髓白血病原始细胞的相关性。本研究通过流式细胞术（flow cytometry），检测了初诊（new diagnosed, ND）、复发难治（relapsed-refractory, RR）、完全缓解（complete remission, CR）急性髓系白血病患者的CD4+与CD8+ T细胞表面CD25、CD38、CD69及HLA-DR的表达水平，同时检测其骨髓与外周血中调节性T细胞的数量。与正常对照（normal controls, NC）相比，本研究发现外周血中CD4+CD69+ T细胞、CD8+CD69+ T细胞及调节性T细胞的比例显著升高。复发难治组患者的CD8+CD38+ T细胞与CD8+HLA-DR+ T细胞水平，显著高于初诊组、完全缓解组及正常对照组。当急性髓系白血病患者达到完全缓解时，其体内调节性T细胞比例可恢复至正常水平。此外，急性髓系白血病原始细胞与CD8+CD25+ T细胞或调节性T细胞仅存在微弱的正相关，而与CD4+CD69+ T细胞则呈微弱的负相关。T细胞与调节性T细胞的异常活化可能参与初诊及复发难治型急性髓系白血病的病理机制。本研究结果提示，CD8+CD38+ T细胞与CD8+HLA-DR+ T细胞可作为急性髓系白血病患者复发难治的潜在生物标志物。进一步而言，调节性T细胞可作为评估急性髓系白血病患者预后的临床指标。