Stasi Roberto, Cooper Nichola, Del Poeta Giovanni, Stipa Elisa, Laura Evangelista Maria, Abruzzese Elisabetta, Amadori Sergio
Department of Medical Sciences, Ospedale Regina Apostolorum, Albano Laziale, Rome, Italy.
Blood. 2008 Aug 15;112(4):1147-50. doi: 10.1182/blood-2007-12-129262. Epub 2008 Mar 28.
The effects of B-cell depletion with rituximab on regulatory T cells (Tregs) have not been determined. We investigated Tregs in patients receiving rituximab for chronic idiopathic thrombocytopenic purpura (ITP). The peripheral blood Tregs, identified as CD4+FOXP3+ T cells, were measured by flow cytometry prior to and after the immunotherapy. In addition, Tregs were analyzed for their usage of the T-cell receptor (TCR) beta-variable (VB) region gene as well as their regulatory function as assessed by cell proliferation assays. Pretreatment data revealed a reduced number and a defective suppressive capacity of Tregs in ITP patients compared with control individuals. In addition, Tregs showed a polyclonal spectratype. Patients, particularly responders, showed restored numbers of Tregs as well as a restored regulatory function upon treatment with rituximab. These results indicate that patients with active ITP have a defective T regulatory cell compartment that can be modulated by a B cell-targeted therapy.
利妥昔单抗清除B细胞对调节性T细胞（Tregs）的影响尚未明确。我们研究了接受利妥昔单抗治疗慢性特发性血小板减少性紫癜（ITP）患者的Tregs。通过流式细胞术在免疫治疗前后测量外周血中被鉴定为CD4+FOXP3+ T细胞的Tregs。此外，分析Tregs的T细胞受体（TCR）β可变（VB）区基因使用情况以及通过细胞增殖试验评估的调节功能。治疗前数据显示，与对照个体相比，ITP患者的Tregs数量减少且抑制能力缺陷。此外，Tregs表现出多克隆谱型。患者，尤其是有反应者，在接受利妥昔单抗治疗后Tregs数量恢复，调节功能也恢复。这些结果表明，活动性ITP患者的T调节细胞区室存在缺陷，可通过靶向B细胞的疗法进行调节。
