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.
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We wish to thank M. Battaglia (DRI, Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute) for helpful scientific discussions and critical revision of the manuscript and we thank L. Passerini (HSR-TIGET, Division of Regenerative Medicine, Stem Cells and Gene Therapy, San Raffaele Scientific Institute) for providing human CD25bright T cell samples. This work was supported by Telethon Foundation 'Comitato Telethon Fondazione Onlus' Core Grant OSR-TIGET project E2 (Rome) to S.G. and M.-G.R. N.G. was supported by an EMBO long-term postdoctoral fellowship. S.H. was supported by the 'Jung-Stiftung', 'Stiftung Experimentelle Biomedizin' and the Deutsche Forschungsgemeinschaft (DFG) (HU 1714/3-1). R.A.F. is an investigator of the Howard Hughes Medical Institute.
The authors declare no competing financial interests.
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Gagliani, N., Magnani, C., Huber, S. et al. Coexpression of CD49b and LAG-3 identifies human and mouse T regulatory type 1 cells. Nat Med 19, 739–746 (2013). https://doi.org/10.1038/nm.3179
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