title: Coexpression of CD49b and LAG-3 identifies human and mouse T regulatory type 1 cells.
abstract: 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.
authors.affiliation: San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), Division of Regenerative Medicine, Stem Cells and Gene Therapy, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Gagliani
authors.forename: Chiara F
authors.initials: CF
authors.lastname: Magnani
authors.forename: Samuel
authors.initials: S
authors.lastname: Huber
authors.forename: Monica E
authors.initials: ME
authors.lastname: Gianolini
authors.forename: Mauro
authors.initials: M
authors.lastname: Pala
authors.forename: Paula
authors.initials: P
authors.lastname: Licona-Limon
authors.forename: Binggege
authors.initials: B
authors.lastname: Guo
authors.forename: De'Broski R
authors.initials: DR
authors.lastname: Herbert
authors.forename: Alessandro
authors.initials: A
authors.lastname: Bulfone
authors.forename: Filippo
authors.initials: F
authors.lastname: Trentini
authors.forename: Clelia
authors.initials: C
authors.lastname: Di Serio
authors.forename: Rosa
authors.initials: R
authors.lastname: Bacchetta
authors.forename: Marco
authors.initials: M
authors.lastname: Andreani
authors.forename: Leonie
authors.initials: L
authors.lastname: Brockmann
authors.forename: Silvia
authors.initials: S
authors.lastname: Gregori
authors.forename: Richard A
authors.initials: RA
authors.lastname: Flavell
authors.forename: Maria-Grazia
authors.initials: MG
authors.lastname: Roncarolo
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000032:analysis* / Q000235:genetics; D002469:Cell Separation; D006801:Humans; D039421:Integrin alpha2 / Q000032:analysis*; D051379:Mice; D008810:Mice, Inbred C57BL; D009559:Nippostrongylus; D017206:Strongylida Infections / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000737:chemistry / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology; D059467:Transcriptome; D000093322:Lymphocyte Activation Gene 3 Protein
chemical_list: D015703:Antigens, CD; D039421:Integrin alpha2; D000093322:Lymphocyte Activation Gene 3 Protein