Coexpression of CD25 and CD27 identifies FoxP3+ regulatory T cells in inflamed synovia.
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.
Ruprecht
Claudia R
CR
Institute for Research in Biomedicine, CH-6500 Bellinzona, Switzerland.
Gattorno
Marco
M
Ferlito
Francesca
F
Gregorio
Andrea
A
Martini
Alberto
A
Lanzavecchia
Antonio
A
Sallusto
Federica
F
D001171:Arthritis, Juvenile / Q000276:immunology* / Q000473:pathology; D015415:Biomarkers / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000032:analysis / Q000276:immunology*; D051858:Forkhead Transcription Factors; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000032:analysis / Q000276:immunology*; D013582:Synovial Fluid / Q000166:cytology / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000032:analysis / Q000276:immunology*
D015415:Biomarkers; D016207:Cytokines; D004268:DNA-Binding Proteins; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D015375:Receptors, Interleukin-2; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7