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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.
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“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]
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“These include the T effector cells, but not the CD4CD25FOXP3 regulatory T cells (Tregs), which are distinguished by low expression of IL-7Ra (11, 12).”
BackgroundInfluentialRegulatory roles of IL-10–producing human follicular T cells
Cañete, P. F., Sweet, R. A., González-Figueroa, P., Papa, I., Ohkura, N., Bolton, H. A., Roco, J. A., Cuenca, M., Bassett, K., Sayın, I., et al. (2019) · The Journal of Experimental Medicine · doi:10.1084/jem.20190493 · Cited by 89
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“Because CD4CD25 T cells in HIV-infected patients may include activated T cells or cells that up-regulated CD25 in response to IL-2 treatment, we sought to quantify Treg by analyzing the proportion of CD4CD25 and CD4CD25 T cells expressing low levels of CD127 and the transcription factor FOXP3 (16, 17) (Fig.”
BackgroundCook, L. E., Munier, C. M. L., Seddiki, N., van Bockel, D. J., Ontiveros, N., Hardy, M. Y., Gillies, J. K., Levings, M. K., Reid, H. H., Petersen, J., et al. (2017) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2017.02.015 · Cited by 85
Self-citationEx vivo expansion of CD4+CD25+ T regulatory cells for immunosuppressive therapy
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“Surprisingly, Tregs do not undergo homeostatic expansion on their own, and they do not express receptor (43,44,96).”
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HDAC6 selective inhibition of melanoma patient T-cells augments anti-tumor characteristics
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The progress and prospect of regulatory T cells in autoimmune diseases
Zhang, X., Olsen, N. J., & Zheng, S. G. (2020) · Journal of Autoimmunity · doi:10.1016/j.jaut.2020.102461 · Cited by 87
CAR-T cell therapy: developments, challenges and expanded applications from cancer to autoimmunity
Kong, Y., Li, J., Zhao, X., Wu, Y., & Chen, L. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1519671 · Cited by 96
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“Regulatory activity is associated with sustained expression of FoxP3 and low levels of CD127, the interleukin (IL)-7 receptor (12, 13).”
Le, K.-S., Thibult, M., Just-Landi, S., Pastor, S., Gondois‐Rey, F., Granjeaud, S., Broussais, F., Bouabdallah, R., Colisson, R., Caux, C., et al. (2016) · Cancer Research · doi:10.1158/0008-5472.can-15-0589 · Cited by 92
“Thus our results corroborate previous investigations (41,42) suggesting that the CD25CD127 combination is useful for Tregs identification.”
ResultRegulatory T cells in solid organ transplantation
Atif, M., Conti, F., Gorochov, G., Oo, Y. H., & Miyara, M. (2020) · Clinical & Translational Immunology · doi:10.1002/cti2.1099 · Cited by 85
“Whilst the mechanism for this was not delineated, this indicates that the link between FOXP3 expression and the CD4CD25CD127 phenotype is not as direct as previously described.(45) This is important from a clinical perspective as current in-human trial protocols are”
BackgroundChowdhury, A., Estrada, P. M. D. R., Tharp, G. K., Trible, R. P., Amara, R. R., Chahroudi, A., Reyes‐Terán, G., Bosinger, S. E., & Silvestri, G. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1402701 · Cited by 83
Li, Q., Zhai, Z., Xu, X., Shen, Y., Zhang, A., Sun, Z., Liu, H., Geng, L., & Wang, Y. (2010) · Leukemia Research · doi:10.1016/j.leukres.2010.03.017 · Cited by 83
Engela, A. U., Baan, C. C., Dor, F. J. M. F., Weimar, W., & Hoogduijn, M. J. (2012) · Frontiers in Immunology · doi:10.3389/fimmu.2012.00126 · Cited by 82
“(2006). CD4+CD25bright+ regulatory T cells can mediate donor nonreactivity in long-term immunosuppressed kidney allograft patients.”
BackgroundInfluentialFrequency and function of regulatory T cells after ischaemic stroke in humans
Yan, J., Read, S. J., Henderson, R. D., Hull, R., O’Sullivan, J. D., McCombe, P., & Greer, J. M. (2012) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2011.12.019 · Cited by 82
“Previously we have reported that the frequency of activated T cells is increased in the peripheral blood of human subjects on days 7 and 21 after acute ischaemic stroke, and have also observed an increase in the frequency of CD4+CD25hi putative Tregs (Yan et al., 2009).”
InfluentialBelarif, L., Mary, C., Jacquemont, L., Le, H., Danger, R., Hervouet, J., Minault, D., Thépenier, V., Nerrière‐Daguin, V., Nguyen, E., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-06804-y · Cited by 79
Hall, B. M., Verma, N. D., Tran, G. T., & Hodgkinson, S. J. (2011) · Current Opinion in Immunology · doi:10.1016/j.coi.2011.07.012 · Cited by 86
Functional defect in regulatory T cells in myasthenia gravis
Thiruppathi, M., Rowin, J., Jiang, Q. L., Sheng, J. R., Prabhakar, B. S., & Meriggioli, M. N. (2012) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2012.06840.x · Cited by 81
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“correlates inversely with Foxp3 and Treg suppressive function; hence Tregs are now defined as CD4CD25CD127Foxp3 cells.(12) Failure of Tregs to suppress effector cells is a typical feature of autoimmunity, including AIH, leading to studies exploring the use of either polyclonal(13,14) or antigen-specific Tregs as cellu…”
BackgroundKlein, S. M., Kretz, C. C., Krammer, P. H., & Kuhn, A. (2009) · Journal of Investigative Dermatology · doi:10.1038/jid.2009.313 · Cited by 79
Ménétrier‐Caux, C., Curiel, T. J., Faget, J., Manuel, M., Caux, C., & Zou, W. (2012) · Targeted Oncology · doi:10.1007/s11523-012-0208-y · Cited by 79
The role of regulatory T cells in neurodegenerative diseases
HeFeng, F. Q., & Balling, R. (2012) · WIREs Systems Biology and Medicine · doi:10.1002/wsbm.1187 · Cited by 80
Cytokine Signaling in the Development and Homeostasis of Regulatory T cellsPreprint
Toomer, K. H., & Malek, T. R. (2017) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a028597 · Cited by 80
“Mature Tregs have traditionally been considered to express uniformly low levels of CD127, which should render them largely insensitive to IL-7-mediated effects (Liu et al. 2006; Seddiki et al. 2006).”
BackgroundMenart, B., RUTTER, R. R., Nowotny, B., Rosenbauer, J., Koliaki, C. C., KAHL, S., Simon, M., Szendroedi, J., Schloot, N. C., Roden, M., et al. (2014) · Diabetes Care · doi:10.2337/dc14-0316 · Cited by 82
“Subsets of Th cells (CD4+) were gated for surface expression of CD25, the IL-2 receptor a-chain, which is expressed in association with CD127, the a-chain of the receptor of IL-7 (14,19).”
BackgroundInfluentialClinical tolerance in allogeneic hematopoietic stem cell transplantation
Roncarolo, M., Gregori, S., Lucarelli, B., Ciceri, F., & Bacchetta, R. (2011) · Immunological Reviews · doi:10.1111/j.1600-065x.2011.01010.x · Cited by 81
T cell‐mediated immunoregulation in the gastrointestinal tract
Saurer, L., & Mueller, C. (2009) · Allergy · doi:10.1111/j.1398-9995.2009.01965.x · Cited by 81
“Concomitant use of additional markers such as absence of CD127 (49, 50) or high CTLA-4 (51) and MHCII (52) expression could provide valuable information although neither will guarantee an unequivocal”
BackgroundTargeting regulatory T cells to improve vaccine immunogenicity in early life
Ndure, J., & Flanagan, K. L. (2014) · Frontiers in Microbiology · doi:10.3389/fmicb.2014.00477 · Cited by 78
“Human FOXP3+ Tregs also tend to express low levels of the IL-7 receptor CD127 (Liu et al., 2006; Seddiki et al., 2006).”
BackgroundWild, C. A., Brandau, S., Lotfi, R., Mattheis, S., Gu, X., Lang, S., & Bergmann, C. (2012) · Oral Oncology · doi:10.1016/j.oraloncology.2011.12.009 · Cited by 77
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“We have defined Treg cells using a combination of phenotypic markers that better delineate Treg cells [35–38].”
BackgroundMethodA Longitudinal Study of Immune Cells in Severe COVID-19 Patients
Payen, D. M., Cravat, M., Maadadi, H., Didelot, C., Prosic, L., Dupuis, C., Losser, M.-R., & Bittencourt, M. D. C. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.580250 · Cited by 77
Good cell, bad cell: Flow cytometry reveals T‐cell subsets important in HIV disease
Chattopadhyay, P. K., & Roederer, M. (2010) · Cytometry Part A · doi:10.1002/cyto.a.20905 · Cited by 78
“In this regard, the measurement of only a couple of key markers (e.g., CD127, CD57) may be sufficient to describe the maturational status of T-cells in HIV1 individuals.”
BackgroundInfluentialGITR+ regulatory T cells in the treatment of autoimmune diseases
Petrillo, M. G., Ronchetti, S., Ricci, E., Alunno, A., Gerli, R., Nocentini, G., & Riccardi, C. (2014) · Autoimmunity Reviews · doi:10.1016/j.autrev.2014.10.011 · Cited by 79
Kim, Y.-J., & Broxmeyer, H. (2010) · Critical reviews in oncology/hematology · doi:10.1016/j.critrevonc.2010.07.009 · Cited by 71
“The CD127lo phenotype highly correlates with expression of FoxP3 within the CD4+CD25+ population [100].”
BackgroundRegulatory T cells Versus Th17: Differentiation of Th17 Versus Treg, Are They Mutually Exclusive?
Zheng, S. G. (2012) · Springer eBooks · doi:10.1007/978-3-0348-0522-3_6 · Cited by 76
“A better approach for the identification of human Treg cells is to target the CD4+CD25+CD127-/low population [3].”
BackgroundBiaso, I. D., Maio, L. D., Bugarin, C., Gaipa, G., Dander, E., Balduzzi, A., Parma, M., D’Amico, G., Perseghin, P., Biondi, A., et al. (2009) · Transplantation · doi:10.1097/tp.0b013e3181a27a5d · Cited by 76
“Because phosphorylated intracytoplasmic STAT-5 has been described as the pathway most relevantly involved in the process of IL-2-dependent activation of T-regs (6), we characterized its grade of phosphorylation in sorted T-regs gating on the CD127-negative population (n 3), considered a good surface T-reg marker (8),…”
BackgroundSuchard, M. S., Mayne, E. S., Green, V. A., Shalekoff, S., Donninger, S. L., Stevens, W. S., Gray, C. M., & Tiemessen, C. T. (2010) · PLoS ONE · doi:10.1371/journal.pone.0011762 · Cited by 76
“Use of other markers to identify Tregs have varied from study to study and include CD25, Cytotoxic T lymphocyte associated protein 4 (CTLA-4 or CD152), glucocorticoid-induced tumour necrosis factor receptor (GITR), CD27, OX40 ([37], CD44 [38], CD62L [39,40], CD39 [41] and decreased expression of CD127 [42,43,44].”
BackgroundInfluentialNigam, P., Velu, V., Kannanganat, S., Chennareddi, L. S., Kwa, S., Siddiqui, M., & Amara, R. R. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0902955 · Cited by 76
“Similar to human CD4 Tregs (49, 50), CD8 Tregs in rhesus macaques also expressed low levels of CD127 (Fig.”
ResultHeidt, S., Segundo, D. S., Shankar, S., Mittal, S., Muthusamy, A. S. R., Friend, P. J., Fuggle, S. V., & Wood, K. J. (2011) · Transplantation · doi:10.1097/tp.0b013e318218e978 · Cited by 75
“The activation marker CD127 facilitates clear-cut gating, with CD127 T cells being regulatory and CD127 T cells being activated (76, 77).”
BackgroundJandus, C., Bioley, G., Speiser, D. E., & Romero, P. J. (2008) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-008-0507-4 · Cited by 75
Identification of heme oxygenase-1–specific regulatory CD8+ T cells in cancer patients
Andersen, M. H., Sørensen, R. B., Brimnes, M. K., Svane, I. M., Becker, J. C., & Straten, P. T. (2009) · Journal of Clinical Investigation · doi:10.1172/jci38739 · Cited by 75
Hall, B. M. (2015) · Clinical Journal of the American Society of Nephrology · doi:10.2215/cjn.06620714 · Cited by 81
“Tregs have low expression of CD127, and depletion of CD127hi cells is used to enrich Tregs and eliminate activated effector CD41CD251 T cells (47).”
BackgroundRegulatory T-Cell Therapy in the Induction of Transplant Tolerance
Edozie, F. C., Nova‐Lamperti, E., Povoleri, G. A. M., Scottà, C., John, S., Lombardi, G., & Afzali, B. (2014) · Transplantation · doi:10.1097/tp.0000000000000243 · Cited by 74
“Although the IL-7R>-chain is highly expressed on resting CD4 T cells in healthy human controls, the evidence clearly suggests an inverse relationship between the suppressive capability of Tregs and the expression of CD127 (4, 42, 43); Tregs defined as CD4CD25CD127 Tregs are highly suppressive and express the greatest…”
BackgroundRegulatory T cells in COVID-19
Wang, H., Wang, Z., Cao, W., Wu, Q., Yuan, Y., & Zhang, X. (2021) · Aging and Disease · doi:10.14336/ad.2021.0709 · Cited by 77
Increased Airway T Regulatory Cells in Asthmatic Subjects
Smyth, L. J. C., Eustace, A., Kolsum, U., Blaikley, J., & Singh, D. (2010) · CHEST Journal · doi:10.1378/chest.09-3079 · Cited by 74
Pulmonary CCL18 Recruits Human Regulatory T Cells
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Imbalance of circulating Tfr/Tfh ratio in patients with rheumatoid arthritis
Wang, X., Yang, C., Xu, F. H., Qi, L., Wang, J., & Yang, P. (2018) · Clinical and Experimental Medicine · doi:10.1007/s10238-018-0530-5 · Cited by 74
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Regulatory T cells in HIV infection: pathogenic or protective participants in the immune response?
Groth, B. F. D. S., & LANDAY, A. L. (2008) · AIDS · doi:10.1097/qad.0b013e3282f466da · Cited by 73
Self-citationMacaubas, C., Nguyen, K. D., Deshpande, C., Phillips, C. I., Peck, A., Lee, T. C., Park, J. L., Sandborg, C. I., & Mellins, E. (2009) · Clinical Immunology · doi:10.1016/j.clim.2009.09.010 · Cited by 73
“The number of CD45RA+ Tregs declines with age [31]; however, age distribution was similar among the groups we tested (Table 1).”
BackgroundMethodResultInfluentialSuppressive Influences in the Immune Response to Cancer
Bronte, V., & D, S. M. M. (2008) · Journal of Immunotherapy · doi:10.1097/cji.0b013e3181837276 · Cited by 73
Rühle, P. F., Fietkau, R., Gaipl, U. S., & Frey, B. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17081316 · Cited by 77
Regulatory T Cells: Molecular and Cellular Basis for Immunoregulation
Togashi, Y., & Nishikawa, H. (2017) · Current topics in microbiology and immunology · doi:10.1007/82_2017_58 · Cited by 75
“…low-level expression of CD127 (IL-7 receptor a-chain) were reported to possess FOXP3 expression and suppressive function (Liu et al. 2006; Seddiki et al. 2006), CD127 is also down-regulated following recent activation of naive T cells that also express a low level of FOXP3 (Mazzucchelli…”
BackgroundHigh frequency and proliferation of CD4+FOXP3+ Treg in HIV‐1‐infected patients with low CD4 counts
Bi, X., Suzuki, Y., Gatanaga, H., & Oka, S. (2008) · European Journal of Immunology · doi:10.1002/eji.200838667 · Cited by 73
CD147 (Basigin/Emmprin) identifies FoxP3+CD45RO+CTLA4+-activated human regulatory T cells
Solstad, T., Bains, S. J., Landskron, J., Aandahl, E. M., Thiede, B., Taskén, K., & Torgersen, K. M. (2011) · Blood · doi:10.1182/blood-2011-02-339242 · Cited by 72
Glisic-Milosavljevic, S., Waukau, J., Jailwala, P., Jana, S., KHOO, H., Albertz, H., Woodliff, J. E., Koppen, M., Alemzadeh, R., Hagopian, W., et al. (2007) · PLoS ONE · doi:10.1371/journal.pone.0000146 · Cited by 75
“Recently however, some papers have shown correlation of high expression of FoxP3 and low or no expression of IL-7R alpha (CD127low/-) on the cell surface[13,14] Humans without functional FoxP3 protein have an autoimmune disorder called IPEX with auto-antibodies against a diversity of organs[15].”
BackgroundPereira, L. E., Villinger, F. J., Onlamoon, N., Bryan, P., Cardona, A. C., Pattanapanysat, K., Mori, K., Hagen, S. I., Picker, L. J., & Ansari, A. A. (2007) · Journal of Virology · doi:10.1128/jvi.00026-07 · Cited by 75
“Additional markers include cytotoxic-T-lymphocyte-associated antigen 4, GITR, low levels of the more recently identified Treg marker IL-7 receptor CD127 (26, 27, 37, 43), and, more recently, unique microRNA profiles (9).”
BackgroundInfluentialRegulatory T cells in kidney disease and transplantation
Hu, M., Wang, Y. M., Wang, Y., Zhang, G. Y., Zheng, G., Yi, S., O’Connell, P. J., Harris, D. C. H., & Alexander, S. I. (2016) · Kidney International · doi:10.1016/j.kint.2016.03.022 · Cited by 73
Self-citationFoxP3 isoforms and PD-1 expression by T regulatory cells in multiple sclerosis
Sambucci, M., Gargano, F., Rosa, V. D., Bardi, M. D., Picozza, M., Placido, R., Ruggieri, S., Capone, A., Gasperini, C., Matarese, G., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-21861-5 · Cited by 72
Yang, G., Zhu, Y., Zhang, W., Zhou, D. B., Zhai, C.-C., & Wang, J. (2016) · Veterinary Research · doi:10.1186/s13567-016-0355-8 · Cited by 71
“CD4+CD25+CD127low cells were used as an alternative marker for regulatory T (Treg) cells, in addition to the conventional CD4+CD25+Foxp3+ population [11].”
MethodFc Receptor-Like 3 Protein Expressed on IL-2 Nonresponsive Subset of Human Regulatory T Cells
Nagata, S., Ise, T., & Pastan, I. H. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0802230 · Cited by 70
“Recent searches for nTreg cell markers in human CD4 cells revealed that downregulation of CD127 (IL-7R -chain) is associated with suppressor function in human CD4 cells (24, 25).”
BackgroundStelmaszczyk‐Emmel, A., Zawadzka‐Krajewska, A., Szypowska, A., Kulus, M., & Demkow, U. A. (2013) · International Archives of Allergy and Immunology · doi:10.1159/000350769 · Cited by 72
Adenosine deaminase potentiates the generation of effector, memory, and regulatory CD4+ T cells
Martinez-Navío, J. M., Casanova, V., Pacheco, R., Naval-Macabuhay, I., Climent, N., García, F., Gatell, J. M., Mallol, J., Gallart, T., Lluı́s, C., et al. (2010) · Journal of Leukocyte Biology · doi:10.1189/jlb.1009696 · Cited by 71
“After a CD4 T cell response, reactivated Ag-specific T cells, which are a part of the pool of CD4 CD45RACD45RO memory T cells [3, 4], coordinate a faster, stronger, and longer immune response [5, 6].”
BackgroundAccelerated age-dependent transition of human regulatory T cells to effector memory phenotype
Santner-Nanan, B., Seddiki, N., Zhu, E., Quent, V., Kelleher, A., de St Groth, B. F., & Nanan, R. (2008) · International Immunology · doi:10.1093/intimm/dxm151 · Cited by 70
Self-citationAntigen presentation, autoantibody production, and therapeutic targets in autoimmune liver disease
Horst, A. K., Kumashie, K. G., Neumann, K., Diehl, L., & Tiegs, G. (2020) · Cellular and Molecular Immunology · doi:10.1038/s41423-020-00568-6 · Cited by 73
Zhang, Q., Leong, S. C., McNamara, P. S., Mubarak, A., Malley, R., & Finn, A. H. R. (2011) · PLoS Pathogens · doi:10.1371/journal.ppat.1002175 · Cited by 70
“Up until now, intracellular expression of Foxp3 is still considered the most specific single marker of Treg, although a combination of phenotypic expression of CD4+CD25+CD127 has also been established as a useful marker for natural Treg [4,5].”
Duggleby, R. C., Danby, R., Madrigal, J. A., & Saudemont, A. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00252 · Cited by 73
“While PB Tregs are predominately CD45RA− (approximately 70%) (46, 48), the majority (>80%) of CB Tregs and CD4+ cells express the naive CD45RA+ phenotype (47, 48).”
BackgroundRegulatory T cells in health and disease
Rouse, B. T. (2007) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2007.01836.x · Cited by 70
Combination of rapamycin and IL-2 increases de novo induction of human CD4+CD25+FOXP3+ T cells
Long, S. A., & Buckner, J. H. (2008) · Journal of Autoimmunity · doi:10.1016/j.jaut.2007.12.012 · Cited by 70
“CD25 sorted cells expressed FOXP3 and were CD127, a surface marker associated with functional nTreg [28,29].”
BackgroundLichtenegger, F. S., Mueller, K., Otte, B., Beck, B., Hiddemann, W., Schendel, D. J., & Subklewe, M. S. (2012) · PLoS ONE · doi:10.1371/journal.pone.0044266 · Cited by 74
“However, the combination of FoxP3 expression and absent or low-level surface expression of the IL-7 receptor a (CD127) is helpful to identify human regulatory T cells [43,44].”
BackgroundZhuo, C., Xu, Y., Ying, M., Li, Q., Huang, L., Li, D., Cai, S., & Li, B. (2015) · Immunologic Research · doi:10.1007/s12026-014-8616-y · Cited by 70
“, the IL7 receptor a-chain) was confirmed to be an additional biomarker for CD4?FOXP3? Tregs [37, 38].”
BackgroundWang, H., Peters, T., Sindrilaru, A., Keß, D., Oreshkova, T., Yu, X., Seier, A. M., Schreiber, H. A., Wlaschek, M., Blakytny, R., et al. (2008) · Journal of Clinical Investigation · doi:10.1172/jci34916 · Cited by 67
Angin, M., Kwon, D. S., Streeck, H., Wen, F., King, M., Rezai, A., Law, K., Hongo, T. C., Pyo, A., Trocha, A. K., et al. (2012) · The Journal of Infectious Diseases · doi:10.1093/infdis/jis236 · Cited by 69
“The interleukin 7 (IL-7) receptor-alpha, CD127, has been described as a reliable surface marker for live cell sorting of Tregs [7] (Figure 2A), and we observed a strong correlation between CD4CD25CD127 and CD4CD25 FOXP3 T cells (R = 0.”
BackgroundThe functional and prognostic implications of regulatory T cells in colorectal carcinoma.
Zhang, X., Kelaria, S., Kerstetter, J. C., & Wang, J. (2015) · PubMed Central · doi:10.3978/j.issn.2078-6891.2015.017 · Cited by 70
“Besides Foxp3, there are other surface markers have been found expressed on Tregs, including CTLA-4 (14), LAG3 (15), GITR (16), HLA-DR (17), ICOS (18), and CD127 (19).”
BackgroundHornero, R. A., Betts, G. J., Sawitzki, B., Vogt, K., Harden, P., & Wood, K. J. (2016) · Transplantation · doi:10.1097/tp.0000000000001278 · Cited by 69
“expression through binding the CD127 promoter.(8,9) Human CD25CD127 Treg cells have been demonstrated to be highly suppressive in vivo in a humanized mouse model.”
BackgroundWoods, D. M., Ramakrishnan, R., Laino, A. S., Berglund, A., Walton, K., Betts, B. C., & Weber, J. S. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-1100 · Cited by 66
Verma, N. D., Lam, A. D., Chiu, C., Tran, G. T., Hall, B. M., & Hodgkinson, S. J. (2021) · Scientific Reports · doi:10.1038/s41598-021-88448-5 · Cited by 75
Fogal, B., Yi, T., Wang, C., Rao, D. A., Lebastchi, A. H., Kulkarni, S., Tellides, G., & Pober, J. S. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1003774 · Cited by 70
In Vitro Expansion Improves In Vivo Regulation by CD4+CD25+ Regulatory T Cells
Chai, J., Coe, D., Chen, D., Simpson, E., Dyson, J., & Scott, D. M. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.2.858 · Cited by 67
“One solution is the use of IL7 receptor -chain (CD127) negative Tregs as the input cell population for expansion (14, 15), and to introduce rapamycin to the culture, which appears to selectively suppress the expansion of contaminating effector T cells (13).”
MethodRezvani, A. R., & Storb, R. F. (2008) · Journal of Autoimmunity · doi:10.1016/j.jaut.2007.12.002 · Cited by 67
“Recently, the cell surface marker CD127 has been used in conjunction with CD4 and CD25 to identify a highly suppressive population of T cells; this marker may be a useful substitute for FOXP3, particularly where viable cells are required [34].”
MethodKisielewicz, A., Schaier, M., Schmitt, E., Hug, F., Haensch, G. M., Meuer, S. C., Zeier, M. G., Sohn, C., & Steinborn, A. (2010) · Clinical Immunology · doi:10.1016/j.clim.2010.07.008 · Cited by 67
Seddiki, N., Cook, L. E., Hsu, D. C., Phetsouphanh, C., Brown, K., Xu, Y., Kerr, S. J., Cooper, D. A., Munier, C. M. L., Pett, S. L., et al. (2014) · European Journal of Immunology · doi:10.1002/eji.201344102 · Cited by 64
Self-citationAllergen provocation increases TH2‐cytokines and FOXP3 expression in the asthmatic lung
Thunberg, S., Gafvelin, G., Nord, M., Grönneberg, R., Grünewald, J., Eklúnd, A., & van Hage, M. (2009) · Allergy · doi:10.1111/j.1398-9995.2009.02218.x · Cited by 66
“CD127 negativity, which was introduced after the initiation of our study (23, 24).”
BackgroundChanges in thymic regulatory T-cell maturation from birth to puberty: Differences in atopic children
Tulić, M. K., Andrews, D., Crook, M. L., CHARLES, A. K., Tourigny, M. R., Moqbel, R., & Prescott, S. L. (2011) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2011.10.016 · Cited by 66
Toh, H. C., Wang, W.-W., Chia, W. K., Kvistborg, P., Sun, L. J., Teo, K., Phoon, Y. P., Soe, Y., Tan, S. H., Hee, S. W., et al. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-1537 · Cited by 67
“More recently, CD127 has been shown as an additional marker to define Treg cells (18, 19).”
BackgroundImmunosuppressive Drugs and Tregs
Serres, S. A. D., Sayegh, M. H., & Najafian, N. (2009) · Clinical Journal of the American Society of Nephrology · doi:10.2215/cjn.03180509 · Cited by 66
Regulatory T cells in acute and chronic kidney diseases
Sharma, R., & Kinsey, G. R. (2017) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00236.2017 · Cited by 67
“However, inclusion of IL-7R (CD127) has helped distinguish Tregs from activated T cells, such that CD4 CD25CD127 cells are widely accepted as Tregs with more than 95% of these cells expressing Foxp3 (205).”
BackgroundRegulatory T Cell Stability and Plasticity in Atherosclerosis
Ali, A. J., Makings, J., & Ley, K. (2020) · Cells · doi:10.3390/cells9122665 · Cited by 65
“The majority of CD4+ Tregs are generated in the thymus (tTregs), and others can be generated from peripheral Tcon cells (pTregs). tTregs arise from CD4+CD25+ cells upon engagement of their high-affinity, self-reactive T-cell receptors (TCRs) [9]. tTregs are found primarily in lymphoid tissues and blood [10] and can mi…”
BackgroundInfluentialZemmour, D., Charbonnier, L., Léon, J., Six, E. M., Keleş, S., Delville, M., Benamar, M., Barış, S., Zuber, J., Chen, K., et al. (2021) · Nature Immunology · doi:10.1038/s41590-021-00910-8 · Cited by 65
“Tregs are typically identified by flow cytometry as CD25 hi CD127 lo , a combination that overlaps well with intracellular FOXP3 expression 34 .”
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
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