The Journal of Experimental Medicine
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Published 6 June 2005. doi:10.1084/jem.20050085
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 201, Number 11, 1793-1803
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ARTICLE

 Coexpression of CD25 and CD27 identifies FoxP3+ regulatory T cells in inflamed synovia

Claudia R. Ruprecht1, Marco Gattorno2, Francesca Ferlito2, Andrea Gregorio2, Alberto Martini2,3, Antonio Lanzavecchia1, and Federica Sallusto1

1 Institute for Research in Biomedicine, CH-6500 Bellinzona, Switzerland
2 UO Pediatria II, Istituto G. Gaslini, Largo G. Gaslini
3 Department of Pediatrics, University of Genoa, 16147 Genoa, Italy

CORRESPONDENCE Federica Sallusto: federica.sallusto{at}irb.unisi.ch

A better understanding of the role of CD4+CD25+ regulatory T cells in disease pathogenesis should follow from the discovery of reliable markers capable of discriminating regulatory from activated T cells. We report that the CD4+CD25+ population in synovial fluid of juvenile idiopathic arthritis (JIA) patients comprises both regulatory and effector T cells that can be distinguished by expression of CD27. CD4+CD25+CD27+ cells expressed high amounts of FoxP3 (43% of them being FoxP3+), did not produce interleukin (IL)-2, interferon-{gamma}, or tumor necrosis factor, and suppressed T cell proliferation in vitro, being, on a per cell basis, fourfold more potent than the corresponding peripheral blood population. In contrast, CD4+CD25+CD27– cells expressed low amounts of FoxP3, produced effector cytokines and did not suppress T cell proliferation. After in vitro activation and expansion, regulatory but not conventional T cells maintained high expression of CD27. IL-7 and IL-15 were found to be present in synovial fluid of JIA patients and, when added in vitro, abrogated the suppressive activity of regulatory T cells. Together, these results demonstrate that, when used in conjunction with CD25, CD27 is a useful marker to distinguish regulatory from effector T cells in inflamed tissues and suggest that at these sites IL-7 and IL-15 may interfere with regulatory T cell function.

Abbreviations used: JIA, juvenile idiopathic arthritis; SFMC, synovial fluid mononuclear cell.

C.R. Ruprecht and M. Gattorno contributed equally to this work.


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