Coexpression of CD49b and LAG-3 identifies human and mouse T regulatory type 1 cells

• Published in: Nature medicine Vol. 19; no. 6; pp. 739 - 746
• Main Authors: Gagliani, Nicola, Magnani, Chiara F, Huber, Samuel, Gianolini, Monica E, Pala, Mauro, Licona-Limon, Paula, Guo, Binggege, Herbert, De'Broski R, Bulfone, Alessandro, Trentini, Filippo, Di Serio, Clelia, Bacchetta, Rosa, Andreani, Marco, Brockmann, Leonie, Gregori, Silvia, Flavell, Richard A, Roncarolo, Maria-Grazia
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.06.2013; Nature Publishing Group
• Subjects: 692/53/2423; Animals; Antigen receptors, T cell; Antigens, CD - analysis; Antigens, CD - genetics; Biomedicine; Cancer Research; Cell Separation; Cytokines; Gene expression; Genetic aspects; Genetic markers; Humans; Infectious Diseases; Integrin alpha2 - analysis; Lymphocytes; Metabolic Diseases; Mice; Mice, Inbred C57BL; Molecular Medicine; Neurosciences; Nippostrongylus; Physiological aspects; Receptors; Stem cells; Strongylida Infections - immunology; T cell receptors; T cells; T-Lymphocytes, Regulatory - chemistry; T-Lymphocytes, Regulatory - immunology; Th17 Cells - immunology; Transcriptome; United States; Italy; Germany
• ISSN: 1078-8956; 1546-170X
• DOI: 10.1038/nm.3179

Type 1 regulatory (Tr1) T cells are characterized by their immunosuppressive activity and cytokine secretion profile; however, their isolation and enumeration are limited by the absence of specific markers. Here Richard Flavell, Maria-Grazia Roncarolo and colleagues report that CD49b and LAG-3 are coexpressed by human and mouse Tr1 cells. These markers can be used to isolate Tr1 cells in vitro and in vivo and can be used to quantify Tr1 cells in tolerant subjects. 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.