Published online 3 July 2006 doi:10.1084/jem.20060468
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 203, Number 7, 1693-1700
Expression of interleukin (IL)-2 and IL-7 receptors discriminates between human regulatory and activated T cells
Nabila Seddiki1,2,3,
Brigitte Santner-Nanan4,
Jeff Martinson5,
John Zaunders2,
Sarah Sasson2,
Alan Landay5,
Michael Solomon6,
Warwick Selby6,
Stephen I. Alexander7,
Ralph Nanan4,
Anthony Kelleher2,3, and
Barbara Fazekas de St. Groth1
1 Centenary Institute of Cancer Medicine and Cell Biology, Faculty of Medicine, University of Sydney, Newtown, NSW 2042, Australia
2 Centre for Immunology, St. Vincents Hospital, Darlinghurst, NSW 2010, Australia
3 National Centre in HIV Epidemiology and Clinical Research, University of NSW, Kensington, NSW 2052, Australia
4 Department of Paediatrics, University of Sydney, Western Clinical School, Penrith, NSW 2751, Australia
5 Department of Immunology/Microbiology, Rush University Medical Center, Chicago, IL 60612
6 Department of Gastroenterology, The Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia
7 The Children's Hospital at Westmead, NSW 2145, Australia
CORRESPONDENCE Barbara Fazekas de St. Groth: b.fazekas{at}centenary.usyd.edu.au
Abnormalities in CD4+CD25+Foxp3+ regulatory T (T reg) cells have been implicated in susceptibility to allergic, autoimmune, and immunoinflammatory conditions. However, phenotypic and functional assessment of human T reg cells has been hampered by difficulty in distinguishing between CD25-expressing activated and regulatory T cells. Here, we show that expression of CD127, the
chain of the interleukin-7 receptor, allows an unambiguous flow cytometrybased distinction to be made between CD127lo T reg cells and CD127hi conventional T cells within the CD25+CD45RO+RA effector/memory and CD45RA+RO naive compartments in peripheral blood and lymph node. In healthy volunteers, peripheral blood CD25+CD127lo cells comprised 6.35 ± 0.26% of CD4+ T cells, of which 2.05 ± 0.14% expressed the naive subset marker CD45RA. Expression of FoxP3 protein and the CD127lo phenotype were highly correlated within the CD4+CD25+ population. Moreover, both effector/memory and naive CD25+CD127lo cells manifested suppressive activity in vitro, whereas CD25+CD127hi cells did not. Cell surface expression of CD127 therefore allows accurate estimation of T reg cell numbers and isolation of pure populations for in vitro studies and should contribute to our understanding of regulatory abnormalities in immunopathic diseases.

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-
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-
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-
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-
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-
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-
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[Full Text]
-
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(2007). Expansion and tissue infiltration of an allospecific CD4+CD25+CD45RO+IL-7R{alpha}high cell population in solid organ transplant recipients. J. Exp. Med.
204: 1533-1541
[Abstract]
[Full Text]
-
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(2007). A New Subset of Human Naive CD8+ T Cells Defined by Low Expression of IL-7R{alpha}. J. Immunol.
179: 221-228
[Abstract]
[Full Text]
-
Yates, J., Rovis, F., Mitchell, P., Afzali, B., Tsang, J.-S, Garin, M., Lechler, R., Lombardi, G., Garden, O.
(2007). The maintenance of human CD4+CD25+ regulatory T cell function: IL-2, IL-4, IL-7 and IL-15 preserve optimal suppressive potency in vitro. Int Immunol
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[Abstract]
[Full Text]
-
Demirkiran, A., Bosma, B. M., Kok, A., Baan, C. C., Metselaar, H. J., IJzermans, J. N. M., Tilanus, H. W., Kwekkeboom, J., van der Laan, L. J. W.
(2007). Allosuppressive Donor CD4+CD25+ Regulatory T Cells Detach from the Graft and Circulate in Recipients after Liver Transplantation. J. Immunol.
178: 6066-6072
[Abstract]
[Full Text]
-
Pereira, L. E., Villinger, F., Onlamoon, N., Bryan, P., Cardona, A., Pattanapanysat, K., Mori, K., Hagen, S., Picker, L., Ansari, A. A.
(2007). Simian Immunodeficiency Virus (SIV) Infection Influences the Level and Function of Regulatory T Cells in SIV-Infected Rhesus Macaques but Not SIV-Infected Sooty Mangabeys. J. Virol.
81: 4445-4456
[Abstract]
[Full Text]
-
Huibregtse, I L, van Lent, A U, van Deventer, S J H
(2007). Immunopathogenesis of IBD: insufficient suppressor function in the gut?. Gut
56: 584-592
[Full Text]
-
Allan, S. E., Crome, S. Q., Crellin, N. K., Passerini, L., Steiner, T. S., Bacchetta, R., Roncarolo, M. G., Levings, M. K.
(2007). Activation-induced FOXP3 in human T effector cells does not suppress proliferation or cytokine production. Int Immunol
19: 345-354
[Abstract]
[Full Text]
-
Brusko, T., Wasserfall, C., McGrail, K., Schatz, R., Viener, H. L., Schatz, D., Haller, M., Rockell, J., Gottlieb, P., Clare-Salzler, M., Atkinson, M.
(2007). No Alterations in the Frequency of FOXP3+ Regulatory T-Cells in Type 1 Diabetes. Diabetes
56: 604-612
[Abstract]
[Full Text]
-
Kinter, A., McNally, J., Riggin, L., Jackson, R., Roby, G., Fauci, A. S.
(2007). Suppression of HIV-specific T cell activity by lymph node CD25+ regulatory T cells from HIV-infected individuals. Proc. Natl. Acad. Sci. USA
104: 3390-3395
[Abstract]
[Full Text]
-
Bracci, L., Moschella, F., Sestili, P., La Sorsa, V., Valentini, M., Canini, I., Baccarini, S., Maccari, S., Ramoni, C., Belardelli, F., Proietti, E.
(2007). Cyclophosphamide Enhances the Antitumor Efficacy of Adoptively Transferred Immune Cells through the Induction of Cytokine Expression, B-Cell and T-Cell Homeostatic Proliferation, and Specific Tumor Infiltration. Clin. Cancer Res.
13: 644-653
[Abstract]
[Full Text]
-
Battaglia, M., Stabilini, A., Migliavacca, B., Horejs-Hoeck, J., Kaupper, T., Roncarolo, M.-G.
(2006). Rapamycin Promotes Expansion of Functional CD4+CD25+FOXP3+ Regulatory T Cells of Both Healthy Subjects and Type 1 Diabetic Patients. J. Immunol.
177: 8338-8347
[Abstract]
[Full Text]
-
Zaunders, J. J., Ip, S., Munier, M. L., Kaufmann, D. E., Suzuki, K., Brereton, C., Sasson, S. C., Seddiki, N., Koelsch, K., Landay, A., Grey, P., Finlayson, R., Kaldor, J., Rosenberg, E. S., Walker, B. D., Fazekas de St. Groth, B., Cooper, D. A., Kelleher, A. D., on Behalf of the PHAEDRA Study Team,
(2006). Infection of CD127+ (Interleukin-7 Receptor+) CD4+ Cells and Overexpression of CTLA-4 Are Linked to Loss of Antigen-Specific CD4 T Cells during Primary Human Immunodeficiency Virus Type 1 Infection.. J. Virol.
80: 10162-10172
[Abstract]
[Full Text]