Coexpression of CD49b and LAG-3 identifies human and mouse T regulatory type 1 cells
Coexpression of CD49b and LAG-3 identifies human and mouse T regulatory type 1 cells
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DOI：
10.1038/nm.3179
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发表时间：
2013-06-01
期刊：
影响因子：
82.9
通讯作者：
Roncarolo, Maria-Grazia
中科院分区：
文献类型：
--
作者：
Gagliani, Nicola;Magnani, Chiara F.;Roncarolo, Maria-Grazia
CD 4（+）1型T调节（Tr 1）细胞在外周中被诱导，并且在促进和维持耐受中具有关键作用。缺乏唯一识别Tr 1细胞的表面标记限制了它们的研究和临床应用。通过对人Tr 1细胞克隆的基因表达谱分析，我们鉴定了表面标记物CD 49 b和淋巴细胞活化基因3（LAG-3）在小鼠和人Tr 1细胞上稳定且选择性共表达。我们在肠道炎症和蠕虫感染的小鼠模型以及健康志愿者的外周血中显示了这些标记物的特异性。CD 49 b和LAG-3的共表达使得能够从体外无反应培养物中分离高度抑制性的人Tr 1细胞，并且允许追踪在同种异体造血干细胞移植后产生耐受的受试者的外周血中的Tr 1细胞。这些标记物的使用使得在体内追踪Tr 1细胞和纯化Tr 1细胞用于细胞治疗以诱导或恢复患有免疫介导的疾病的受试者的耐受性成为可能。
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.