The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.
Expression of interleukin (IL)-2 and IL-7 receptors discriminates between human regulatory and activated T cells
Open accessAbstract
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 α chain of the interleukin-7 receptor, allows an unambiguous flow cytometry–based 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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In terms of surface phenotype, the best accepted combination of markers is high expression of the IL-2 receptor α chain (CD25) and low expression of the IL-7R α chain (CD127) [134, 385].”
From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [385]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Sakaguchi, S. (2003) · Annual Review of Immunology · doi:10.1146/annurev.immunol.21.120601.141122 · Cited by 3,315
CD4+CD25high Regulatory Cells in Human Peripheral Blood
Baecher‐Allan, C., Brown, J. A., Freeman, G. J., & Hafler, D. A. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.3.1245 · Cited by 1,889
Loss of Functional Suppression by CD4+CD25+ Regulatory T Cells in Patients with Multiple Sclerosis
Viglietta, V., Baecher‐Allan, C., Weiner, H. L., & Hafler, D. A. (2004) · The Journal of Experimental Medicine · doi:10.1084/jem.20031579 · Cited by 1,858
Ulcerative colitis-like disease in mice with a disrupted interleukin-2 gene
Sadlack, B., Merz, H., Schorle, H., Schimpl, A., Feller, A. C., & Horak, I. D. (1993) · Cell · doi:10.1016/0092-8674(93)80067-o · Cited by 1,744
Lymphopenia in interleukin (IL)-7 gene-deleted mice identifies IL-7 as a nonredundant cytokine
von Freeden-Jeffry, U., Vieira, P., Lucian, L., McNeil, T., Burdach, S. E. G., & Murray, R. (1995) · Journal of Experimental Medicine · doi:10.1084/jem.181.4.1519 · Cited by 1,648
Compromised Function of Regulatory T Cells in Rheumatoid Arthritis and Reversal by Anti-TNFα Therapy
Ehrenstein, M. R., Evans, J. G., Singh, A., Moore, S., Warnes, G., Isenberg, D. A., & Mauri, C. (2004) · The Journal of Experimental Medicine · doi:10.1084/jem.20040165 · Cited by 1,253
Ling, E. M., Smith, T. R. F., Nguyen, X. D., Pridgeon, C., Dallman, M. J., Arbery, J., Carr, V. A., & Robinson, D. S. (2004) · The Lancet · doi:10.1016/s0140-6736(04)15592-x · Cited by 759
Homeostasis and anergy of CD4+CD25+ suppressor T cells in vivo
Gavin, M. A., Clarke, S. R. M., Negrou, E., Gallegos, A. M., & Rudensky, A. Y. (2001) · Nature Immunology · doi:10.1038/ni743 · Cited by 643
Multiple immuno-regulatory defects in type-1 diabetes
Kukreja, A., Cost, G., Marker, J., Zhang, C., Sun, Z., Lin‐Su, K., Ten, S., Sanz, M. M., Exley, M. A., Wilson, B., et al. (2002) · Journal of Clinical Investigation · doi:10.1172/jci13605 · Cited by 640
Analysis of FOXP3 protein expression in human CD4+CD25+ regulatory T cells at the single-cell level
Roncador, G., Brown, P. J., Maestre, L., Hüe, S., Martinez-Torrecuadrada, J. L., Ling, K., Pratap, S., Toms, C., Fox, B. C., Cerundolo, V., et al. (2005) · European Journal of Immunology · doi:10.1002/eji.200526189 · Cited by 592
Flagged first, then by citations
Research works printed but not linked: 1
- 2005, Hum. Immunol., 66, 13
Cited by
Sorted by citations
Items 201–300 of 1,000
Regulatory T‐cell heterogeneity and the cancer immune response
Ward‐Hartstonge, K. A., & Kemp, R. A. (2017) · Clinical & Translational Immunology · doi:10.1038/cti.2017.43 · Cited by 122
Vukmanovic-Stejic, M., Agius, E., Booth, N., Dunne, P. J., Lacy, K. E., Reed, J. R., Sobande, T. O., Kissane, S., Salmon, M., Rustin, M. H., et al. (2008) · Journal of Clinical Investigation · doi:10.1172/jci35834 · Cited by 131
The soluble isoform of CTLA‐4 as a regulator of T‐cell responses
Ward, F. J., Dahal, L. N., Wijesekera, S. K., Abdul-Jawad, S., Kaewarpai, T., Xu, H., Vickers, M. A., & Barker, R. N. (2013) · European Journal of Immunology · doi:10.1002/eji.201242529 · Cited by 133
Boyman, O., Ramsey, C., Kim, D. M., Sprent, J., & Surh, C. D. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.11.7265 · Cited by 135
“Stimulation of Tregs is unlikely because these cells are relatively independent of IL-7 (49, 50).”
BackgroundCell-surface IL-7 receptor expression facilitates the purification of FOXP3+ regulatory T cells
Banham, A. H. (2006) · Trends in Immunology · doi:10.1016/j.it.2006.10.002 · Cited by 131
CD40 ligand and MHC class II expression are essential for human peripheral B cell tolerance
Hervé, M., Isnardi, I., Ng, Y.-S., Bussel, J. B., Ochs, H. D., Cunningham‐Rundles, C., & Meffre, E. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20062287 · Cited by 131
Ammirati, E., Cianflone, D., Banfi, M., Vecchio, V., Palini, A. G., Metrio, M. D., Marenzi, G., Panciroli, C., Tumminello, G., Anzuini, A., et al. (2010) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.110.206813 · Cited by 130
Zhang, Y., Maksimovic, J., Naselli, G., Qian, J., Chopin, M., Blewitt, M. E., Oshlack, A., & Harrison, L. C. (2013) · Blood · doi:10.1182/blood-2013-02-481788 · Cited by 132
Luque‐Campos, N., Contreras-López, R. A., Paredes-Martínez, M. J., Torres, M. J., Bahraoui, S., Wei, M., Espinoza, F., Djouad, F., Elizondo-Vega, R. J., & Luz‐Crawford, P. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00798 · Cited by 132
“Moreover, Treg are characterized by a low expression of CD127 (IL-7 receptor alpha-chain) (113), and a down-regulation of CD127 which is associated with regulatory function acquisition (114).”
BackgroundEngineering interferons and interleukins for cancer immunotherapy
Holder, P. G., Lim, S. A., Huang, C., Sharma, P. A., Dagdas, Y. S., Bulutoglu, B., & Sockolosky, J. T. (2022) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2022.114112 · Cited by 130
Increased CD127 expression on activated FOXP3+CD4+ regulatory T cells
Simonetta, F., Chiali, A., Cordier, C., Urrutia, A., Girault, I., Bloquet, S., Tanchot, C., & Bourgeois, C. (2010) · European Journal of Immunology · doi:10.1002/eji.201040531 · Cited by 129
Thiruppathi, M., Rowin, J., Ganesh, B. B., Sheng, J. R., Prabhakar, B. S., & Meriggioli, M. N. (2012) · Clinical Immunology · doi:10.1016/j.clim.2012.09.012 · Cited by 128
“It has been recently demonstrated that low expression of the IL-7Rα chain (CD127) combined with high expression of CD25 enables better identification and isolation of pure Treg populations with high suppressive functionality [16,17].”
BackgroundLactic acid bacteria differ in their ability to induce functional regulatory T cells in humans
de Roock, S., van Elk, M., van Elk, M., Timmerman, H. M., Rijkers, G. T., Prakken, B. J., Hoekstra, M. O., & de Kleer, I. M. (2009) · Clinical & Experimental Allergy · doi:10.1111/j.1365-2222.2009.03344.x · Cited by 131
Immune cell trafficking from the brain maintains CNS immune tolerance
Mohammad, M. G., Tsai, V. W.-W., Ruitenberg, M. J., Hassanpour, M., Li, H., Hart, P. H., Breit, S. N., Sawchenko, P. E., & Brown, D. A. (2014) · Journal of Clinical Investigation · doi:10.1172/jci71544 · Cited by 135
Divekar, A., Dubey, S., Gangalum, P. R., & Singh, R. R. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.1002218 · Cited by 128
“CD127 expression that inversely correlates with the suppressive function of human Treg cells (27) was also not different between C3H and MRL/lpr mice (Supplemental Fig.”
ResultRegulatory T cells in the central nervous system
Lowther, D. E., & Hafler, D. A. (2012) · Immunological Reviews · doi:10.1111/j.1600-065x.2012.01130.x · Cited by 128
“In humans, the highest CD25-expressing cells are suppressive in vitro (19, 34), and the populations of CD4 T cells that lack surface expression of CD127 are enriched for FoxP3 (35, 36).”
BackgroundImpact of Immune-Modulatory Drugs on Regulatory T Cell
Furukawa, A., Wisel, S. A., & Tang, Q. (2016) · Transplantation · doi:10.1097/tp.0000000000001379 · Cited by 130
“2290 Transplantation ■ November 2016 ■ Volume 100 ■ Number 11 www.transplantjournal.com such as lymphoid tissue-inducer cells and innate lymphocytes,42 are reduced after daclizumab treatment duringmultiple sclerosis (MS) flares.43,44 These immunosuppressive mechanisms may contribute to the positive clinical outcomes o…”
BackgroundFOXP3+ regulatory T cells: Current controversies and future perspectives
Banham, A. H., Powrie, F. M., & Suri‐Payer, E. (2006) · European Journal of Immunology · doi:10.1002/eji.200636459 · Cited by 126
An update on regulatory T cells in transplant tolerance and rejection
Li, X. C., & Turka, L. A. (2010) · Nature Reviews Nephrology · doi:10.1038/nrneph.2010.101 · Cited by 126
“Evidence exists that human CD4 + T REG cells and non-T REG cells can be segregated by differential expression of CD25 and CD127 (the alpha chain of IL-7 receptor) where functional T REG cells are confined exclusively to the CD25 + CD127 − fraction”
BackgroundPeters, J. H., Preijers, F. W. M. B., Woestenenk, R., Hilbrands, L. B., Koenen, H. J. P. M., & Joosten, I. (2008) · PLoS ONE · doi:10.1371/journal.pone.0003161 · Cited by 126
“Recently, it has been described that Tconv express the IL-7 receptor alpha-chain CD127, while Treg cells do not express CD127 [22,23].”
BackgroundResolving the identity myth: Key markers of functional CD4+FoxP3+ regulatory T cells
Chen, X., & Oppenheim, J. J. (2011) · International Immunopharmacology · doi:10.1016/j.intimp.2011.05.018 · Cited by 138
“It is also problematic that activated human CD4+ Teffs can express high levels of CD25 [33].”
BackgroundZhang, B., Zhang, X., Tang, F. L., Zhu, L., Liu, Y., & Lipsky, P. E. (2008) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2007.083543 · Cited by 126
Zhang, X., Mozeleski, B., Lemoine, S., Dériaud, E., Lim, A., Zhivaki, D., Azria, É., Ray, C. L., Roguet, G., Launay, O., et al. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3008748 · Cited by 125
“Activated CD4 T cells also express CD25, but it occurs at much lower levels in these cells than in Treg cells, and this phenotype can be found in both adult and cord blood (21).”
BackgroundJandl, C., Liu, S. M., Cañete, P. F., Warren, J. A., Hughes, W. E., Vogelzang, A., Webster, K. E., Craig, M. E., Uzel, G., Dent, A. L., et al. (2017) · Nature Communications · doi:10.1038/ncomms14647 · Cited by 131
Cell-surface signatures of immune dysfunction risk-stratify critically ill patients: INFECT study
Morris, A. C., Datta, D., Shankar‐Hari, M., Stephen, J., Weir, C. J., Rennie, J., Antonelli, J., Bateman, A. P., Warner, N. L., Judge, K. W., et al. (2018) · Intensive Care Medicine · doi:10.1007/s00134-018-5247-0 · Cited by 124
Aging and human CD4+ regulatory T cells
Hwang, K.-A., Kim, H., & Kang, I. (2009) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2009.06.003 · Cited by 125
Indoleamine 2,3-dioxygenase specific, cytotoxic T cells as immune regulators
Sørensen, R. B., Hadrup, S. R., Svane, I. M., Hjortsø, M. C., Straten, P. T., & Andersen, M. H. (2010) · Blood · doi:10.1182/blood-2010-06-288498 · Cited by 126
Lim, A. Y. F., Tan, D. B. A., Price, P., Kamarulzaman, A., Tan, H.-Y., JAMES, I. R., & French, M. A. (2007) · AIDS · doi:10.1097/qad.0b013e32825eab8b · Cited by 123
“Recent studies show that CD25CD4 T cells expressing low amounts of CD127 (a chain of the interleukin-7 receptor) have the molecular and functional characteristics of Treg cells in healthy control donors and type 1 diabetics [7,8].”
BackgroundResultRole of T cells in graft rejection and transplantation tolerance
Issa, F., Șchiopu, A., & Wood, K. J. (2009) · Expert Review of Clinical Immunology · doi:10.1586/eci.09.64 · Cited by 126
Dunham, R. M., Cervasi, B., Brenchley, J. M., Albrecht, H., Weintrob, A., Sumpter, B., Engram, J. C., Gordon, S. N., Klatt, N. R., Frank, I., et al. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.8.5582 · Cited by 121
Seddiki, N., Sasson, S. C., Santner‐Nanan, B., Munier, C. M. L., van Bockel, D. J., Ip, S., Marriott, D., Pett, S. L., Nanan, R. K. H., Cooper, D. A., et al. (2009) · European Journal of Immunology · doi:10.1002/eji.200838630 · Cited by 121
Self-citationRegulatory T Cells: Serious Contenders in the Promise for Immunological Tolerance in Transplantation
Safinia, N., Scottà, C., Vaikunthanathan, T., Lechler, R. I., & Lombardi, G. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00438 · Cited by 119
“Despite such studies in favor of CD45RA+ cells, one drawback is that the number of naïve Tregs decline in the peripheral blood with age (72) and hence isolation based on this approach may prove to be impractical.”
BackgroundNicholaou, T., Ebert, L. M., Davis, I. D., McArthur, G. A., Jackson, H. M., Dimopoulos, N., Tan, B. S., Maraskovsky, E., Miloradovic, L., Hopkins, W., et al. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-2484 · Cited by 119
Autoimmune hepatitis: new paradigms in the pathogenesis, diagnosis, and management
Oo, Y. H., Hübscher, S. G., & Adams, D. (2010) · Hepatology International · doi:10.1007/s12072-010-9183-5 · Cited by 121
“Peripheral tolerance is maintained by a subset of CD4 T cells that express high levels of the IL-2 receptor CD25 and low levels of the Il-7 receptor (CD127) known as regulatory T cells (Treg) [93–96].”
BackgroundCutting Edge: Programmed Death-1 Defines CD8+CD122+ T Cells as Regulatory versus Memory T Cells
Dai, H., Ni, W., Zhang, S., Moore, Y., Wan, F., & Dai, Z. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.1000661 · Cited by 117
“Given that expression of CD25 (IL2Ra) and CD127 on CD4 T cells discriminates between Treg cells and conventional T cells with CD25CD127(2) being CD4 Treg cells (24), expression of CD122 (IL-2Rb) and CD127 on CD8 cells may define Treg and memory T cells.”
Braudeau, C., Racapé, M., Giral, M., Louis, S., Moreau, A., Berthelot, L., Heslan, M., Ashton‐Chess, J., Soulillou, J., & Brouard, S. (2007) · Transplant International · doi:10.1111/j.1432-2277.2007.00537.x · Cited by 116
“effectors, the CD4CD25 T cells were additionally selected on the basis of their absence of CD127 expression, a characteristic of human Treg [24].”
BackgroundIn vitro effects of cyclosporine a and tacrolimus on regulatory T-cell proliferation and function
Miroux, C., Morales, O., Ghazal, K., Othman, S. B., de Launoit, Y., Pancré, V., Conti, F., & Delhem, N. (2012) · Transplantation · doi:10.1097/tp.0b013e3182590d8f · Cited by 117
“The transcription factor FoxP3, expressed by Tregs, seems to be a master gene controlling Treg development (8), most FoxP3 Tregs being CD127/low (9, 10).”
BackgroundDerhovanessian, E., Adams, V., Hähnel, K., Groeger, A., Pandha, H., Ward, S., & Pawelec, G. (2009) · International Journal of Cancer · doi:10.1002/ijc.24497 · Cited by 122
Regulatory T Cell and Forkhead Box Protein 3 as Modulators of Immune Homeostasis
Pereira, L. M. S., Gomes, S. T. M., Ishak, R., & Vallinoto, A. C. R. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00605 · Cited by 121
“Basal expression levels of the IL-7 receptor (CD127) are characteristic of this cell population, and it is, therefore, used to distinguish them from other lymphocytes (57).”
BackgroundRegulatory T‐cells in systemic lupus erythematosus and rheumatoid arthritis
Chavele, K.-M., & Ehrenstein, M. R. (2011) · FEBS Letters · doi:10.1016/j.febslet.2011.07.043 · Cited by 114
“Venigalla et al. showed that CD4+CD25 T-responder cells isolated from patients with active SLE were significantly less sensitive than those from patients with inactive SLE to the suppressive function of autologous or normal donor CD4+CD25+CD127dim T-cells.”
BackgroundInfluentialYates, J., Rovis, F., Mitchell, P., Afzali, B., Tsang, J. Y., Garin, M. I., Lechler, R. I., Lombardi, G., & Garden, O. A. (2007) · International Immunology · doi:10.1093/intimm/dxm047 · Cited by 115
T regulatory cells in cancer: recent advances and therapeutic potential
Elkord, E., Alcantar-Orozco, E., Dovedi, S. J., Tran, D. Q., Hawkins, R. E., & Gilham, D. E. (2010) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.2010.529126 · Cited by 113
“Two studies demonstrated that CD127 expression is downregulated on human Tregs, inversely correlating with the expression of FoxP3 [50,51].”
BackgroundRegulatory T Cells in Mycobacterium tuberculosis Infection
Cardona, P., & Cardona, P.-J. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02139 · Cited by 113
“In the case of CD127, the α chain of the IL-7 receptor, low to undetectable expression levels have also been used to identify Tregs among CD4CD25 cells (25).”
MethodRegulatory T cells and immunodeficiency in mycosis fungoides and Sézary syndrome
Krejsgaard, T., Ødum, N., Geisler, C., Wasik, M. A., & Woetmann, A. (2011) · Leukemia · doi:10.1038/leu.2011.237 · Cited by 113
Regulatory T Cells in Systemic Sclerosis
Frantz, C., Auffray, C., Avouac, J., & Allanore, Y. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02356 · Cited by 110
“Later, it was shown that low expression of CD127, the α-chain of the IL7 receptor, acts as an additional marker for the characterization of Treg cells among CD4+CD25high T cells (25, 26).”
BackgroundThe Role of the Immune System in Cutaneous Squamous Cell Carcinoma
Bottomley, M. J., Thomson, J., Harwood, C. A., & Leigh, I. M. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20082009 · Cited by 109
Fueling Cancer Immunotherapy With Common Gamma Chain Cytokines
Dwyer, C. J., Knochelmann, H. M., Smith, A. S., Wyatt, M. M., Rivera, G. O. R., Arhontoulis, D. C., Bartee, E., Li, Z., Rubinstein, M. P., & Paulos, C. M. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00263 · Cited by 107
“Unlike IL-2, IL-7 does not induce Treg proliferation, as IL-7Rα is expressed at low levels on this suppressive lymphocyte population (132, 133).”
BackgroundFernandez, M. A., Puttur, F. K., Wang, Y. M., Howden, W., Alexander, S. I., & Jones, C. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.3.1556 · Cited by 109
“Initially defined by the expression of CD25, the further identification of the X-linked transcription factor Foxp3 demonstrated a clear lineage of thymically derived self-Ag-restricted T cells that limited autoimmune disease (2, 3).”
BackgroundSelf-citationFollicular regulatory T cells impair follicular T helper cells in HIV and SIV infection
Miles, B., Miller, S. M., Folkvord, J. M., Kimball, A. K., Chamanian, M., Meditz, A. L., Arends, T., McCarter, M. D., Levy, D. N., Rakasz, E. G., et al. (2015) · Nature Communications · doi:10.1038/ncomms9608 · Cited by 108
Preferential Migration of T Regulatory Cells Induced by IL-16
McFadden, C., Morgan, R. K., Rahangdale, S., Green, D. S., Yamasaki, H., & Cruikshank, W. W. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.10.6439 · Cited by 110
“To address this, we sorted CD4 T cells using CD127 as a marker of non-Treg cells as recently reported (31, 32).”
MethodEnhanced formation and survival of CD4+CD25hiFoxp3+T-cells in chronic lymphocytic leukemia
Jak, M., Jak, M., Mous, R., Remmerswaal, E. B. M., Spijker, R., Jaspers, A., Yagüe, A., Eldering, E., van Lier, R. A. W., & van Oers, M. H. J. (2009) · Leukemia & lymphoma/Leukemia and lymphoma · doi:10.1080/10428190902803677 · Cited by 108
“This phenotype has been associated with Foxp3 expression and regulatory function [19,20].”
BackgroundMichel, L., Berthelot, L., Pettré, S., Wiertlewski, S., Lefrère, F., Braudeau, C., Brouard, S., Soulillou, J., & Laplaud, D. A. (2008) · Journal of Clinical Investigation · doi:10.1172/jci35365 · Cited by 110
Giatromanolaki, A. N., Bates, G. J., Koukourakis, M. I., Sivridis, E., Gatter, K. C., Harris, A. L., & Banham, A. H. (2008) · Gynecologic Oncology · doi:10.1016/j.ygyno.2008.04.021 · Cited by 108
Lamprecht, B., Kreher, S., Anagnostopoulos, I., Jöhrens, K., Monteleone, G., Jundt, F., Stein, H., Janz, M., Dörken, B., & Mathas, S. (2008) · Blood · doi:10.1182/blood-2008-01-134783 · Cited by 107
The imbalance between regulatory and IL-17-secreting CD4+ T cells in lupus patients
Ma, J., Yu, J., Tao, X., Cai, L., Wang, J., & Zheng, S. G. (2010) · Clinical Rheumatology · doi:10.1007/s10067-010-1510-7 · Cited by 107
Menard, C., Ghiringhelli, F., Roux, S., Chaput, N., Mateus, C., Grohmann, U., Caillat‐Zucman, S., Zitvogel, L., & Robert, C. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-4797 · Cited by 106
Shaw, J. M., Hunt, P. W., Critchfield, J. W., McConnell, D. H., Garcia, J. C., Pollard, R. B., Somsouk, M., Deeks, S. G., & Shacklett, B. L. (2011) · Journal of Virology · doi:10.1128/jvi.05608-11 · Cited by 104
“Additionally, a previous study of Treg found that the CD25hi CD127lo phenotype appeared to be reflecting the high levels of immune activation found in viremic progressors and did not correlate with levels of FOXP3 CD25hi T cells (21).”
BackgroundInfluentialImpaired in vitro regulatory T cell function associated with Wiskott–Aldrich syndrome
Adriani, M., Aoki, J., Horai, R., Thornton, A. M., Konno, A., Kirby, M., Anderson, S. M., Siegel, R. M., Candotti, F., & Schwartzberg, P. L. (2007) · Clinical Immunology · doi:10.1016/j.clim.2007.02.001 · Cited by 105
“Because in humans, FOXP3 can be transiently expressed in some activated CD4+ cells (27), we examined CD127 expression on sorted populations, which is inversely correlated with Treg function (28,29).”
BackgroundWang, W., Hodkinson, P. S., McLaren, F., MacKinnon, A. C., Wallace, W. A., Howie, S., & Sethi, T. (2012) · International Journal of Cancer · doi:10.1002/ijc.27613 · Cited by 104
“CD127, the a-chain of the IL-7 receptor, has been shown to be a marker to discriminate between human CD4þ regulatory and activated T cells, and its expression inversely correlates with FOXP3 and suppressive function.(14,15) Helios protein, a member of the Ikaros transcription factor family, has been reported to distin…”
BackgroundLiberal, R., Grant, C. R., Holder, B. S., Cardone, J., Martínez‐Llordella, M., Ma, Y., Heneghan, M. A., Mieli‐Vergani, G., Vergani, D., & Longhi, M. S. (2015) · Hepatology · doi:10.1002/hep.27884 · Cited by 103
Moving to tolerance: Clinical application of T regulatory cells
McMurchy, A. N., Bushell, A., Levings, M. K., & Wood, K. J. (2011) · Seminars in Immunology · doi:10.1016/j.smim.2011.04.001 · Cited by 101
“The second combination also uses CD4 and CD25 but includes an antibody to CD127 (IL-7Rα) on the basis that in human nTreg, there is a reciprocal expression of CD127 and FOXP3 and thus CD127 provides a sort-able surrogate maker for FOXP3+ nTreg [62, 63].”
BackgroundPhysical exercise modulates the homeostasis of human regulatory T cells
Weinhold, M., Shimabukuro‐Vornhagen, A., Franke, A., Theurich, S., Wahl, P., Hallek, M. J., Schmidt, A., Schinköthe, T., Mester, J., von Bergwelt‐Baildon, M., et al. (2016) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2015.10.035 · Cited by 102
Esendağlı, G., Bruderek, K., Goldmann, T., Busche, A., Branscheid, D., Vollmer, E., & Brandau, S. (2007) · Lung Cancer · doi:10.1016/j.lungcan.2007.07.022 · Cited by 100
Tabares, P., Berr, S., Römer, P. S., Chuvpilo, S., Matskevich, A. A., Tyrsin, D., Fedotov, Y., Einsele, H., Tony, H., & Hünig, T. (2014) · European Journal of Immunology · doi:10.1002/eji.201343967 · Cited by 97
Golding, A., Hasni, S., Illei, G. G., & Shevach, E. M. (2013) · Arthritis & Rheumatism · doi:10.1002/art.38119 · Cited by 99
“As an alternative approach to the analysis of Treg cells from SLE patients, we used the wellestablished phenotype CD25highCD127− (17).”
MethodInfluentialJiang, T. T., Chaturvedi, V., Ertelt, J. M., Kinder, J. M., Clark, D. R., Valent, A. M., Xin, L., & Way, S. S. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1400498 · Cited by 104
“However, although high-level CD25 expression has consistently identified cells with suppressive properties in vitro, their ability to restrain effector T cell activation in vivo remains incompletely defined, and diminished CD127 expression that more uniformly identifies suppressive cells has not been consistently used…”
BackgroundRegulatory T cell frequency and modulation of IFN-gamma and IL-17 in active and latent tuberculosis
Marín, N. D., París, S. C., Marín, V. M. V., Rojas, C. A., Rojas, M., & García, L. F. (2010) · Tuberculosis · doi:10.1016/j.tube.2010.05.003 · Cited by 99
Tangye, S. G., Pillay, B. A., Randall, K. L., Avery, D. T., Phan, T. G., Gray, P. E., Ziegler, J. B., Smart, J. M., Peake, J., Arkwright, P. D., et al. (2016) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2016.07.016 · Cited by 102
The Proportion of Regulatory T Cells in Patients with Rheumatoid Arthritis: A Meta-Analysis
Morita, T., Shima, Y., Wing, J. B., Sakaguchi, S., Ogata, A., & Kumanogoh, A. (2016) · PLoS ONE · doi:10.1371/journal.pone.0162306 · Cited by 98
“One reason for this may be that the CD25 positive population contains FOXP3 negative effecter T cells [56].”
BackgroundImmune Reconstitution after Allogeneic Hematopoietic Cell Transplantation in Children
de Koning, C. C. H., Plantinga, M., Besseling, P. J., Boelens, J. J., & Nierkens, S. (2015) · Transplantation and Cellular Therapy · doi:10.1016/j.bbmt.2015.08.028 · Cited by 99
“Tregs are identi fi ed by a [71] with intracellular expression of the transcription factor FoxP3 [72].”
Tumor Microenvironment and Immune Escape
Ferrone, S., & Whiteside, T. L. (2007) · Surgical Oncology Clinics of North America · doi:10.1016/j.soc.2007.08.004 · Cited by 99
Young, N. T., Waller, E. C. P., Patel, R., Roghanian, A., Austyn, J. M., & Trowsdale, J. (2007) · Blood · doi:10.1182/blood-2007-05-089771 · Cited by 98
Homeostasis and Function of Regulatory T Cells in HIV/SIV Infection
Moreno‐Fernandez, M. E., Presicce, P., & Chougnet, C. A. (2012) · Journal of Virology · doi:10.1128/jvi.00993-12 · Cited by 98
“Initially characterized in the mouse by the constitutive expression of the interleukin-2R (IL2R ) chain (CD25) (76), Tregs were shown in further studies to express low levels of the IL-7R chain (CD127) (52, 81).”
BackgroundModulating T‐cell homeostasis with IL‐7: preclinical and clinical studies
Capitini, C. M., Chisti, A. A., & Mackall, C. L. (2009) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2009.02085.x · Cited by 98
Regulatory T Cells and Transplantation Tolerance
Jiang, S., Lechler, R. I., He, X.-S., & Huang, J.-F. (2006) · Human Immunology · doi:10.1016/j.humimm.2006.07.013 · Cited by 98
Tan, D., Yong, Y., Tan, H., Kamarulzaman, A., Tan, L., Lim, A. Y. F., JAMES, I. R., French, M. A., & Price, P. (2008) · HIV Medicine · doi:10.1111/j.1468-1293.2008.00565.x · Cited by 98
Regulatory T Cells Are Reduced During Anti-CD25 Antibody Treatment of Multiple Sclerosis
Oh, U., Blevins, G., Griffith, C., Richert, N. D., Maric, D., Lee, C. R., McFarland, H. F., & Jacobson, S. (2009) · Archives of Neurology · doi:10.1001/archneurol.2009.16 · Cited by 97
Fayyad‐Kazan, H., Rouas, R., Fayyad‐Kazan, M., Badran, R., Zein, N. E., Lewalle, P., Najar, M., Hamade, E., Jebbawi, F., Merimi, M., et al. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.337154 · Cited by 104
T-regulatory cells in systemic lupus erythematosus
Cava, A. L. (2008) · Lupus · doi:10.1177/0961203308090028 · Cited by 96
Raimondi, G., Sumpter, T. L., Matta, B. M., Pillai, M., Corbitt, N., Yoram Vodovotz, B., Wang, Z., & Thomson, A. W. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0900936 · Cited by 96
“Additionally, an alternative strategy based on reduced expression of CD127 (IL7R) on Treg has been proposed (32, 33).”
BackgroundTran, T.-A., de Herve, M.-G. D. G., Hendel, H., Dembelé, B., le Névot, E., Abbed, K., Pallier, C., Goujard, C., Gasnault, J., Delfraissy, J., et al. (2008) · PLoS ONE · doi:10.1371/journal.pone.0003305 · Cited by 105
“1A) as previously reported [24,25] and suppressed conventional CD4 T-cell proliferation following”
BackgroundMethodRegulatory T Helper Cells in Pregnancy and their Roles in Systemic versus Local Immune Tolerance
Ernerudh, J., Berg, G. E., & Mjösberg, J. (2011) · American Journal of Reproductive Immunology · doi:10.1111/j.1600-0897.2011.01049.x · Cited by 98
Regulatory T cells for tolerance
Kawai, K., Uchiyama, M., Hester, J., Wood, K. J., & Issa, F. (2017) · Human Immunology · doi:10.1016/j.humimm.2017.12.013 · Cited by 99
Subcellular localization of FOXP 3 in human regulatory and nonregulatory T cells
Magg, T., Mannert, J., Ellwart, J. W., Schmid, I., & Albert, M. H. (2012) · European Journal of Immunology · doi:10.1002/eji.201141838 · Cited by 101
The Dendritic Cell-Regulatory T Lymphocyte Crosstalk Contributes to Tumor-Induced Tolerance
Janikashvili, N., Bonnotte, B., Katsanis, E., & Larmonier, N. (2011) · Clinical and Developmental Immunology · doi:10.1155/2011/430394 · Cited by 98
“CD127 expression has indeed been reported to inversely correlate with FoxP3 expression and the suppressive function of Treg [113, 114].”
BackgroundBetts, B. C., Abdel-Wahab, O. I., Curran, S. A., Angelo, E. T. S., Koppikar, P., Heller, G., Levine, R. L., & Young, J. W. (2011) · Blood · doi:10.1182/blood-2011-06-363408 · Cited by 95
Miyara, M., Wing, K., & Sakaguchi, S. (2009) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2009.03.001 · Cited by 100
Wüest, T., Willette‐Brown, J., Durum, S. K., & Hurwitz, A. A. (2008) · Journal of Leukocyte Biology · doi:10.1189/jlb.1107778 · Cited by 95
CD8+ regulatory T cells, their suppressive mechanisms, and regulation in cancer
Wang, R.-F. (2008) · Human Immunology · doi:10.1016/j.humimm.2008.08.276 · Cited by 93
Kawashiri, S., Kawakami, A., Okada, A., Koga, T., Tamai, M., Yamasaki, S., Nakamura, H., Origuchi, T., Ida, H., & Eguchi, K. (2011) · The Journal of Rheumatology · doi:10.3899/jrheum.110283 · Cited by 93
“CD127, distinguishes Treg cells from activated T cells demonstrating a significant correlation between the FOXP3 and CD127 phenotype at the same time that it functionally suppresses the CD127 population [12, 13].”
BackgroundAltered homeostasis of CD4+ FoxP3+regulatory T‐cell subpopulations in systemic lupus erythematosus
Suen, J., Li, H., Jong, Y., Chiang, B., & Yen, J. (2008) · Immunology · doi:10.1111/j.1365-2567.2008.02937.x · Cited by 93
Association of Serum Interleukin-7 Levels With the Development of Acute Graft-Versus-Host Disease
Dean, R. M., Fry, T. J., Mackall, C. L., Steinberg, S. M., Hakim, F. T., Fowler, D. H., Odom, J., Foley, J., Gress, R. E., & Bishop, M. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2008.17.1314 · Cited by 92
“IL-7 is produced constitutively by stromal cells and consumed by the available pool of resting T cells, all of which express the IL-7 receptor (IL-7R) at high levels except for CD4 CD25 regulatory T cells.(4) Systemic IL-7 levels increase during periods of lymphopenia to maintain naïve T-cell homeostasis and support t…”
BackgroundEnumeration of human peripheral blood dendritic cells throughout the life
Orsini, G., Legitimo, A., Failli, A., Massei, F., Biver, P., & Consolini, R. (2012) · International Immunology · doi:10.1093/intimm/dxs006 · Cited by 91
The targeting of immunosuppressive mechanisms in hematological malignancies
Andersen, M. H. (2014) · Leukemia · doi:10.1038/leu.2014.108 · Cited by 91
Induced regulatory T cells in inhibitory microenvironments created by cancer
Whiteside, T. L. (2014) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.2014.927432 · Cited by 97
“Among T cells, Tregs express high levels of IL-2R (CD25) and are dependent on IL-2 for their development, growth and suppressor functions [45-47].”
BackgroundAn In Vitro System to Model the Establishment and Reactivation of HIV-1 Latency
Marini, A., Harper, J. M., & Romerio, F. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.11.7713 · Cited by 93
“Based on these features, we concluded that the population of CD25 cells contained CD4 CD45RA CD127FoxP3 natural naive regulatory cells described previously (19, 20).”
BackgroundJenabian, M.-A., Seddiki, N., Yatim, A., Carrière, M., Hulin, A., Younas, M., Ghadimi, E., Kök, A., Routy, J., Tremblay, A., et al. (2013) · PLoS Pathogens · doi:10.1371/journal.ppat.1003319 · Cited by 90
“(CD127) [2–5].”
Self-citationVenet, F., Lepape, A., & Monneret, G. (2011) · Critical Care · doi:10.1186/cc10333 · Cited by 91
Correa‐Rocha, R., Pérez, A., Lorente, R., Ferrando‐Martínez, S., Leal, M., Gurbindo, D., & Muñoz‐Fernández, M. Á. (2012) · Pediatric Research · doi:10.1038/pr.2012.6 · Cited by 93
“We analyzed the levels of this population identified as CD4+CD25+CD127low cells in neonates (Figure 2a (13)).”
BackgroundLonghi, M. S., Mitry, R. R., Samyn, M., Scalori, A., Hussain, M. J., Quaglia, A., Mieli‐Vergani, G., Ma, Y., & Vergani, D. (2009) · Hepatology · doi:10.1002/hep.22914 · Cited by 89
Metadata
- Authors
- Seddiki, N., Santner-Nanan, B., Martinson, J., Zaunders, J., Sasson, S., Landay, A., Solomon, M., Selby, W., Alexander, S. I., Nanan, R., Kelleher, A., & de St. Groth, B. F.
- Affiliations
- The University of Sydney (AU)
- 4Department of Paediatrics, University of Sydney, Western Clinical School, Penrith, NSW 2751, Australia
- Rush University Medical Center (US)
- St Vincent's Hospital Sydney (AU)
- Royal Prince Alfred Hospital (AU)
- Children's Hospital at Westmead (AU)
- UNSW Sydney (AU)
- 1Centenary Institute of Cancer Medicine and Cell Biology, Faculty of Medicine, University of Sydney, Newtown, NSW 2042, Australia
- ORCID
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2006-07-03
- Volume
- 203
- Issue
- 7
- Pages
- 1693-1700
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC2118333
- OpenAlex
- W2168628806
- Cited by
- 1,512
- References
- 30
- Citations by year
- 2026: 18 · 2025: 25 · 2024: 32 · 2023: 32 · 2022: 44 · 2021: 49 · 2020: 58 · 2019: 75 · 2018: 51 · 2017: 64 · 2016: 74 · 2015: 63 · 2014: 87 · 2013: 92 · 2012: 116
- FWCI
- 45.91
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- UNSWorks (University of New South Wales, Sydney, Australia) (submittedVersion, cc-by-nc-nd)
- Funders
- Crohn's and Colitis Foundation of America
- Crohn's and Colitis Foundation
- Medical Research Council
- National Health and Medical Research Council
- National Institute of Allergy and Infectious Diseases (P01AI055793, AI55793, U19AI055793)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
- Keywords
- regulatory T cells, CD127, interleukin-2 receptor, Foxp3, CD25, CD4+ T cells, naive T cells, effector memory T cells
- MeSH terms
- Adult, Humans, Infant, Newborn, Lymphocyte Activation, Receptors, Interleukin-2, T-Lymphocyte Subsets, Receptors, Interleukin-7, T-Lymphocytes, Regulatory
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
