San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), Division of Regenerative Medicine, Stem Cells and Gene Therapy, San Raffaele Scientific Institute, Milan, Italy.
Nat Med. 2013 Jun;19(6):739-46. doi: 10.1038/nm.3179. Epub 2013 Apr 28.
CD4(+) type 1 T regulatory (Tr1) cells are induced in the periphery and have a pivotal role in promoting and maintaining tolerance. The absence of surface markers that uniquely identify Tr1 cells has limited their study and clinical applications. By gene expression profiling of human Tr1 cell clones, we identified the surface markers CD49b and lymphocyte activation gene 3 (LAG-3) as being stably and selectively coexpressed on mouse and human Tr1 cells. We showed the specificity of these markers in mouse models of intestinal inflammation and helminth infection and in the peripheral blood of healthy volunteers. The coexpression of CD49b and LAG-3 enables the isolation of highly suppressive human Tr1 cells from in vitro anergized cultures and allows the tracking of Tr1 cells in the peripheral blood of subjects who developed tolerance after allogeneic hematopoietic stem cell transplantation. The use of these markers makes it feasible to track Tr1 cells in vivo and purify Tr1 cells for cell therapy to induce or restore tolerance in subjects with immune-mediated diseases.
CD4(+) 型 1 调节性 T 细胞（Tr1）在周围组织中被诱导产生，在促进和维持免疫耐受方面发挥着关键作用。由于缺乏能够唯一识别 Tr1 细胞的表面标志物，限制了对其的研究和临床应用。通过对人类 Tr1 细胞克隆的基因表达谱分析，我们发现表面标志物 CD49b 和淋巴细胞激活基因 3（LAG-3）在小鼠和人类 Tr1 细胞上稳定且选择性地共同表达。我们在肠道炎症和寄生虫感染的小鼠模型以及健康志愿者的外周血中证明了这些标志物的特异性。CD49b 和 LAG-3 的共表达可从体外失能培养物中分离出高度抑制性的人类 Tr1 细胞，并可追踪在接受异基因造血干细胞移植后产生耐受的受试者外周血中的 Tr1 细胞。这些标志物的使用使得在体内追踪 Tr1 细胞并纯化 Tr1 细胞进行细胞治疗以诱导或恢复免疫介导性疾病患者的耐受成为可能。
