Introduction: Advanced chronic lymphocytic leukemia (CLL) is accompanied by increased circulating regulatory T cells (Tregs) and increased susceptibility to severe infections, which were also shown to entail a striking induction of FOXP3 expression in Tregs. As homeostasis of the most suppressive CD45RA−FOXP3highactivated Treg (aTreg) subset differs, it is critical to analyse homeostatic signalling in Treg subsets. Materials and Methods: In this study, by using conventional and imaging flow cytometry, we monitored STAT5 signalling/phosphorylation (pSTAT5) and investigated Treg subsets in relation to the Binet stage, the total tumor mass score (TTM) and the disease course during a follow-up of 37 patients with CLL. Results: The aTreg percentage was significantly increased among CD4+T cells from patients with advanced disease and significantly correlated with the TTM. A subgroup of patients with higher aTreg percentages among CD4+FOXP3+T cells at the start of therapy was characterised by more frequent episodes of severe infections during follow-up. Conclusions: The results suggesting that an aTreg fraction could represent a possible marker of a severe disease course with infectious complications. Augmented homeostatic STAT5 signalling could support aTreg expansion, as higher pSTAT5 levels were significantly correlated with an increased aTreg frequency among CD4+FOXP3+T cells during the follow-up of patients on therapy, as well as following SARS-CoV-2 antigen-specific stimulation in vitro.
引言：晚期慢性淋巴细胞白血病（CLL）常伴随循环调节性T细胞（Tregs）的增加以及对严重感染的易感性增高，研究还显示这会导致Tregs中FOXP3表达的显著诱导。鉴于最具抑制性的CD45RA−FOXP3高表达活化Treg（aTreg）亚群的稳态调控机制存在差异，分析Treg亚群的稳态信号传导至关重要。材料与方法：本研究采用常规流式细胞术与成像流式细胞术，监测了37例CLL患者随访期间的STAT5信号传导/磷酸化（pSTAT5）水平，并分析了Treg亚群与Binet分期、总肿瘤负荷评分（TTM）及疾病进程的关系。结果：晚期患者CD4+T细胞中aTreg比例显著升高，且与TTM呈显著正相关。治疗开始时CD4+FOXP3+T细胞中aTreg比例较高的患者亚组，在随访期间出现严重感染发作的频率更高。结论：研究结果表明aTreg比例可能作为预测伴有感染并发症的重症病程的潜在标志物。增强的稳态STAT5信号可能支持aTreg扩增——在治疗患者的随访期间，较高的pSTAT5水平与CD4+FOXP3+T细胞中aTreg频率增加显著相关；体外SARS-CoV-2抗原特异性刺激后也观察到相同趋势。
肿瘤(癌症)患者之家