Regulatory T (T reg) cells are critical regulators of immune tolerance. Most T reg cells are defined based on expression of CD4, CD25, and the transcription factor, FoxP3. However, these markers have proven problematic for uniquely defining this specialized T cell subset in humans. We found that the IL-7 receptor (CD127) is down-regulated on a subset of CD4+ T cells in peripheral blood. We demonstrate that the majority of these cells are FoxP3+, including those that express low levels or no CD25. A combination of CD4, CD25, and CD127 resulted in a highly purified population of T reg cells accounting for significantly more cells that previously identified based on other cell surface markers. These cells were highly suppressive in functional suppressor assays. In fact, cells separated based solely on CD4 and CD127 expression were anergic and, although representing at least three times the number of cells (including both CD25+CD4+ and CD25−CD4+ T cell subsets), were as suppressive as the “classic” CD4+CD25hi T reg cell subset. Finally, we show that CD127 can be used to quantitate T reg cell subsets in individuals with type 1 diabetes supporting the use of CD127 as a biomarker for human T reg cells.
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10 July 2006
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July 03 2006
CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells
Weihong Liu,
Weihong Liu
1UCSF Diabetes Center, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143
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Amy L. Putnam,
Amy L. Putnam
1UCSF Diabetes Center, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143
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Zhou Xu-yu,
Zhou Xu-yu
1UCSF Diabetes Center, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143
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Gregory L. Szot,
Gregory L. Szot
1UCSF Diabetes Center, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143
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Michael R. Lee,
Michael R. Lee
1UCSF Diabetes Center, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143
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Shirley Zhu,
Shirley Zhu
1UCSF Diabetes Center, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143
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Peter A. Gottlieb,
Peter A. Gottlieb
2Department of Pediatrics and Medicine, University of Colorado Health Sciences Center, Denver, CO 80262
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Philipp Kapranov,
Philipp Kapranov
3Affymetrix, Inc., Santa Clara, CA 95051
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Thomas R. Gingeras,
Thomas R. Gingeras
3Affymetrix, Inc., Santa Clara, CA 95051
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Barbara Fazekas de St. Groth,
Barbara Fazekas de St. Groth
4Centenary Institute of Cancer Medicine and Cell Biology, Faculty of Medicine, University of Sydney, New South Wales 2042 Australia
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Carol Clayberger,
Carol Clayberger
5Department of Pediatrics, Stanford University, Stanford, CA 94035
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David M. Soper,
David M. Soper
6Immunology Program, Benaroya Research Institute and Department of Immunology, University of Washington School of Medicine, Seattle, WA 98101
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Steven F. Ziegler,
Steven F. Ziegler
6Immunology Program, Benaroya Research Institute and Department of Immunology, University of Washington School of Medicine, Seattle, WA 98101
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Jeffrey A. Bluestone
Jeffrey A. Bluestone
1UCSF Diabetes Center, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143
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Weihong Liu
1UCSF Diabetes Center, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143
Amy L. Putnam
1UCSF Diabetes Center, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143
Zhou Xu-yu
1UCSF Diabetes Center, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143
Gregory L. Szot
1UCSF Diabetes Center, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143
Michael R. Lee
1UCSF Diabetes Center, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143
Shirley Zhu
1UCSF Diabetes Center, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143
Peter A. Gottlieb
2Department of Pediatrics and Medicine, University of Colorado Health Sciences Center, Denver, CO 80262
Philipp Kapranov
3Affymetrix, Inc., Santa Clara, CA 95051
Thomas R. Gingeras
3Affymetrix, Inc., Santa Clara, CA 95051
Barbara Fazekas de St. Groth
4Centenary Institute of Cancer Medicine and Cell Biology, Faculty of Medicine, University of Sydney, New South Wales 2042 Australia
Carol Clayberger
5Department of Pediatrics, Stanford University, Stanford, CA 94035
David M. Soper
6Immunology Program, Benaroya Research Institute and Department of Immunology, University of Washington School of Medicine, Seattle, WA 98101
Steven F. Ziegler
6Immunology Program, Benaroya Research Institute and Department of Immunology, University of Washington School of Medicine, Seattle, WA 98101
Jeffrey A. Bluestone
1UCSF Diabetes Center, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143
CORRESPONDENCE Jeffrey A. Bluestone: [email protected]
Abbreviations used: ChIP, chromatin immunoprecipitation; MLR, mixed lymphocyte response; T1D, type 1 diabetes; T reg, regulatory T.
W. Liu and A.L. Putnam contributed equally to this work.
Received:
April 10 2006
Accepted:
June 06 2006
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2006
J Exp Med (2006) 203 (7): 1701–1711.
Article history
Received:
April 10 2006
Accepted:
June 06 2006
Citation
Weihong Liu, Amy L. Putnam, Zhou Xu-yu, Gregory L. Szot, Michael R. Lee, Shirley Zhu, Peter A. Gottlieb, Philipp Kapranov, Thomas R. Gingeras, Barbara Fazekas de St. Groth, Carol Clayberger, David M. Soper, Steven F. Ziegler, Jeffrey A. Bluestone; CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells . J Exp Med 10 July 2006; 203 (7): 1701–1711. doi: https://doi.org/10.1084/jem.20060772
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