The Journal of Experimental Medicine
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Published online 3 July 2006 doi:10.1084/jem.20060772
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 203, Number 7, 1701-1711
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ARTICLE

 CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells

Weihong Liu1, Amy L. Putnam1, Zhou Xu-yu1, Gregory L. Szot1, Michael R. Lee1, Shirley Zhu1, Peter A. Gottlieb2, Philipp Kapranov3, Thomas R. Gingeras3, Barbara Fazekas de St. Groth4, Carol Clayberger5, David M. Soper6, Steven F. Ziegler6, and Jeffrey A. Bluestone1

1 UCSF Diabetes Center, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143
2 Department of Pediatrics and Medicine, University of Colorado Health Sciences Center, Denver, CO 80262
3 Affymetrix, Inc., Santa Clara, CA 95051
4 Centenary Institute of Cancer Medicine and Cell Biology, Faculty of Medicine, University of Sydney, New South Wales 2042 Australia
5 Department of Pediatrics, Stanford University, Stanford, CA 94035
6 Immunology Program, Benaroya Research Institute and Department of Immunology, University of Washington School of Medicine, Seattle, WA 98101

CORRESPONDENCE Jeffrey A. Bluestone: jbluest{at}diabetes.ucsf.edu

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.

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.


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