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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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Skartsis, N., Peng, Y., Ferreira, L. M. R., Nguyen, V. Q., Ronin, É., Müller, Y. D., Vincenti, F. G., & Tang, Q. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.783282 · Cited by 67
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“This definition of Treg has been well established in samples from healthy controls.(16,17) We validated correct Treg identification within CD3-positive/CD4-positive/CD25-positive/CD127-negative cells in a subgroup of patients with CLL by detecting high intracellular expression levels of FoxP3 and the ability to suppre…”
BackgroundCirculating immune cells in multiple sclerosis
Jones, A. P., Kermode, A. G., Lucas, R. M., Carroll, W. M., Nolan, D. A., & Hart, P. H. (2016) · Clinical & Experimental Immunology · doi:10.1111/cei.12878 · Cited by 65
“As FoxP3 expression inversely correlates with cell surface CD127 expression (37, 38), Treg may be phenotyped as CD4+CD25+FoxP3+ T cells,”
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F lt3 ligand expands CD 4+ F ox P 3+ regulatory T cells in human subjects
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Mikulková, Z., Praksová, P., Štourač, P., Bednařík, J., Strajtova, L., Pacasová, R., Bělobrádková, J., Dítě, P., & Michálek, J. (2010) · Cellular Immunology · doi:10.1016/j.cellimm.2010.02.002 · Cited by 66
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BackgroundCD4 + CD25 low GITR + cells: A novel human CD4 + T‐cell population with regulatory activity
Bianchini, R., Bistoni, O., Alunno, A., Petrillo, M. G., Ronchetti, S., Sportoletti, P., Bartoloni, E., Nocentini, G., Gerli, R., & Riccardi, C. (2011) · European Journal of Immunology · doi:10.1002/eji.201040943 · Cited by 64
López, P., González-Rodríguez, I., Sánchez, B., Ruas‐Madiedo, P., Suárez, A., Margollés, A., & Gueimonde, M. (2012) · Applied and Environmental Microbiology · doi:10.1128/aem.07581-11 · Cited by 64
“Figure 1 shows that before culture, freshly isolated CD4 CD25high cells, the natural Treg (nTreg) cell population, in addition to showing high FOXP3 and low CD127 levels, expressed CCR6, CCR4, and CCR3, but not CXCR3, so we used the CCR6 CCR4 CCR3 CXCR3 phenotype as a chemokine receptor Treg marker (Fig.”
BackgroundInfluentialCD101 Surface Expression Discriminates Potency Among Murine FoxP3+ Regulatory T Cells
Fernández, I., Zeiser, R., Karsunky, H., Kambham, N., Beilhack, A., Söderström, K., Negrin, R. S., & Engleman, E. G. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.5.2808 · Cited by 64
Regulatory T cells: tolerance induction in solid organ transplantation
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Harnessing the power of regulatory T‐cells to control autoimmune diabetes: overview and perspective
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Viisanen, T., Gazali, A. M., Ihantola, E., Ekman, I., Näntö‐Salonen, K., Veijola, R., Toppari, J., Knip, M., Ilonen, J., & Kinnunen, T. T. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00019 · Cited by 64
Liechti, T., & Roederer, M. (2019) · Cytometry Part A · doi:10.1002/cyto.a.23853 · Cited by 68
“expression of the transcription factor Forkhead Box P3 (FoxP3), which plays an important role in immune regulation (27,28).”
BackgroundPromoting transplantation tolerance; adoptive regulatory T cell therapy
Safinia, N., Leech, J. M., Hernández-Fuentes, M. P., Lechler, R. I., & Lombardi, G. (2012) · Clinical & Experimental Immunology · doi:10.1111/cei.12052 · Cited by 64
Strauss, L., Bergmann, C., & Whiteside, T. L. (2007) · International Journal of Cancer · doi:10.1002/ijc.23001 · Cited by 63
“Reports in the literature suggest that Treg lack CD127, a receptor for IL-7.(18,19) Highly suppressive Treg clones upregulated CD25 (IL2-Ra) and CD122 (IL-2Rb) expression and down-regulated CD132, the IL-2 receptor g chain that is shared by IL-2 and IL-15.”
InfluentialThe role of CD4+CD25hi regulatory T cells in the physiopathogeny of graft-versus-host disease
Cohen, J. L., & Boyer, O. (2006) · Current Opinion in Immunology · doi:10.1016/j.coi.2006.07.007 · Cited by 63
CD4+CD25hiCD127low Regulatory T Cells Are Increased in Oral Squamous Cell Carcinoma Patients
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“Markers delineating these cells include CD25, cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), glucocorticoid-induced tumor necrosis factor receptor family-related gene (GITR), lymphocyte activation gene-3 (LAG3), CD127 and forkhead / winged-helix transcription factor box P3 (FOXP3) [26,35–39].”
BackgroundRegulatory T Cells: From Discovery to AutoimmunityPreprint
Kitz, A., Singer, E. R., & Hafler, D. A. (2018) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a029041 · Cited by 71
“This is contrary to Tregs, which display a high expression of CD25 while they are predominantly negative for CD127 (CD25 CD127) (Liu et al. 2006; Seddiki et al. 2006).”
BackgroundResultInfluentialRegulatory T cells in Graves’ disease
Pan, D., Shin, Y., Gopalakrishnan, G., Hennessey, J. V., & DeGroot, L. J. (2009) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2009.03544.x · Cited by 63
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Disrupted regulatory T cell homeostasis in inflammatory bowel diseases
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Regulatory T cells: first steps of clinical application in solid organ transplantation
van der Net, J. B., Bushell, A., Wood, K. J., & Harden, P. (2015) · Transplant International · doi:10.1111/tri.12608 · Cited by 60
“The surface expression of CD127 is inversely correlated with FOXP3 expression [9,10] and has allowed for refinement of the nTreg phenotype with studies showing that CD4 + CD25 + CD127lo cells are approximately 5 times more potent than CD4 + CD25hi cells [11].”
BackgroundTargeting tumor-infiltrating tregs for improved antitumor responses
Qin, D., Zhang, Y., Shu, P., Lei, Y., Li, X., & Wang, Y. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1325946 · Cited by 63
“The expression of CD127 is negatively correlated with the suppressive function of Treg and the expression of FOXP3, some research teams suggested using CD127 (the alpha subunit of the IL-7 receptor) in combination with CD25 and CD4 as markers for human Tregs (30, 31).”
BackgroundVaricella Zoster–Specific CD4+Foxp3+ T Cells Accumulate after Cutaneous Antigen Challenge in Humans
Vukmanovic‐Stejic, M., Sandhu, D., Sobande, T. O., Agius, E., Lacy, K. E., Riddell, N. E., Montez, S., Dintwe, O., Scriba, T. J., Breuer, J., et al. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1201331 · Cited by 62
“CD4Foxp3 T cells display a Treg phenotype Human CD4 T cells can transiently upregulate Foxp3 after activation; however, these recently activated T cells do not express a typical CD25CD127CD39 Treg phenotype (7, 30, 31).”
BackgroundIanni, M. D., Papa, B. D., Cecchini, D., Bonifacio, E. E., Moretti, L., Zei, T., Ostini, R. I., Falzetti, F., Fontana, L., Tagliapietra, G. A., et al. (2009) · Clinical & Experimental Immunology · doi:10.1111/j.1365-2249.2009.03901.x · Cited by 61
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“In this study, we focused on two types of regulatory T cells (Tregs), which were defined according to literature: CD4CD25CD127 Tregs and IL-10 Tregs [35,36].”
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T-Cell Immunosenescence and Inflammatory Response in Atomic Bomb Survivors
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Juffroy, O., Bugault, F., Lambotte, O., Landires, I., Viard, J., Niel, L., Fontanet, A. L., Delfraissy, J., Thèze, J., & Chakrabarti, L. A. (2009) · Journal of Virology · doi:10.1128/jvi.01475-09 · Cited by 61
“Indeed, Tregs are characterized by a constitutively high level of CD25/IL-2R expression and a conversely low expression of CD127/IL-7R (47, 72).”
BackgroundWalter, G. J., Fleskens, V., Frederiksen, K. S., Rajasekhar, M., Menon, B. S., Gerwien, J. G., Evans, H. G., & Taams, L. S. (2015) · Arthritis & Rheumatology · doi:10.1002/art.39408 · Cited by 61
“cells (34) in the PB from patients with RA were determined within the CD31CD41CD45RO1 (memory) T cell compartment, since CD41CD25 Treg cells are predominantly memory cells (35) and because T cells in the SF are of the CD45RO1 memory phenotype (36).”
BackgroundTai, W. M. D., Yong, W. P., Lim, C., Low, L., Tham, C. K., Koh, T. S., Ng, Q. S., Wang, W., Wang, L. Z., Hartano, S., et al. (2016) · Annals of Oncology · doi:10.1093/annonc/mdw415 · Cited by 61
Breast Cancer Immunology and Immunotherapy
de la Cruz‐Merino, L., Chiesa, M., Caballero, R., Rojo, F., Carrión, N. P., Carrasco, F. H., & Sánchez‐Margalet, V. (2016) · International review of cytology · doi:10.1016/bs.ircmb.2016.09.008 · Cited by 63
Purroy, C., Fairchild, R. L., Tanaka, T., Baldwin, W. M., Manrique, J., Madsen, J. C., Colvin, R. B., Alessandrini, A., Blazar, B. R., Fribourg, M., et al. (2017) · Journal of the American Society of Nephrology · doi:10.1681/asn.2016101100 · Cited by 62
Sonigra, A., Nel, H. J., Wehr, P., Ramnoruth, N., Patel, S. P., van Schie, K. A., Bladen, M. W., Mehdi, A. M., Tesiram, J., Talekar, M., et al. (2022) · JCI Insight · doi:10.1172/jci.insight.160964 · Cited by 60
“In preclinical models of ASIT, peripheral antigen-specific regulatory T cells (Tregs) required T cell receptor (TCR) ligation and were shown to suppress multiple autoreactive T cell specificities through bystander tolerance (5, 6).”
MethodInfluentialVondran, F. W. R., Timrott, K., Tross, J., Kollrich, S., Schwarz, A., Lehner, F., Klempnauer, J., Becker, T., & Schwinzer, R. (2009) · Transplant International · doi:10.1111/j.1432-2277.2009.01013.x · Cited by 62
“Identification of the transcription factor forkhead box P3 (FoxP3) [10] and more recently the down-regulation of the IL-7 receptor (CD127) on Tregs [11,12] have provided adequate tools to do so.”
BackgroundAbdulahad, W. H., Meijer, J. M., Kroese, F. G. M., Meiners, P. M., Vissink, A., Spijkervet, F. K. L., Kallenberg, C. G. M., & Bootsma, H. (2011) · Arthritis & Rheumatism · doi:10.1002/art.30236 · Cited by 60
Mackroth, M. S., Malhotra, I. J., Mungai, P., Koech, D., Muchiri, E. M., & King, C. L. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1001188 · Cited by 60
Increased proportions of functionally impaired regulatory T cell subsets in systemic sclerosis
Ugor, E., Simon, D., Almanzar, G., Pap, R., Najbauer, J., Németh, P., Balogh, P., Prelog, M., Czirják, L., & Berki, T. (2017) · Clinical Immunology · doi:10.1016/j.clim.2017.05.013 · Cited by 60
Lin, Y., Hara, H., Tai, H., Long, C. E., Tokita, D., Yeh, P. C., Ayares, D., Morelli, A. E., & Cooper, D. K. C. (2008) · Transplantation · doi:10.1097/tp.0b013e318188acb0 · Cited by 60
“CD127 may prove to be a biomarker for human Tregs (63, 64), and may facilitate the purification of allo- or pig-reactive Tregs.”
BackgroundInhibitory Effects of Cyclosporine on Human Regulatory T Cells In Vitro
Miroux, C., Moralès, O., Carpentier, A., Dharancy, S., Conti, F., Boleslowski, E., Podevin, P., Auriault, C., Pancré, V., & Delhem, N. (2009) · Transplantation Proceedings · doi:10.1016/j.transproceed.2009.08.043 · Cited by 59
Kahaly, G. J., Shimony, O., Gellman, Y. N., Lytton, S. D., Eshkar-Sebban, L., Rosenblum, N., Refaeli, E., Kassem, S., Ilany, J., & Naor, D. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2010-1424 · Cited by 59
“Quantity of 10,000 events were collected on FACS calibur 500 flow cytometer (BD Biosciences) gated on lymphocytes (based on forward and side scatter) and CD4 and analyzed with CellQuest software version 4.0.2 (BD Biosciences, San Jose, CA) for the Treg cell markers CD25, CD127, and FoxP3.”
ResultInfluentialOtsubo, K., Kanegane, H., Kamachi, Y., Kobayashi, I., Tsuge, I., Imaizumi, M., Sasahara, Y., Hayakawa, A., Nozu, K., Iijima, K., et al. (2011) · Clinical Immunology · doi:10.1016/j.clim.2011.06.006 · Cited by 62
Ukena, S. N., Hoepting, M., Velaga, S., Ivanyi, P., Grosse, J., Baron, U., Ganser, A., & Franzke, A. (2011) · Experimental Hematology · doi:10.1016/j.exphem.2011.08.010 · Cited by 60
“The combinatory targeting of CD127 and CD25 allows the isolation of Treg cells with a high purity [9].”
BackgroundSynovial and Peripheral Blood CD4+FoxP3+ T Cells in Spondyloarthritis
Appel, H., Wu, P., Scheer, R., Kedor, C., Sawitzki, B., Thiel, A., Radbruch, A., Sieper, J., & Syrbe, U. (2011) · The Journal of Rheumatology · doi:10.3899/jrheum.110377 · Cited by 59
Jeffery, H. C., Braitch, M. K., Brown, S., & Oo, Y. H. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00334 · Cited by 60
“org September 2016 | Volume 7 | Article 334 suppressive function of CD4+ Treg (6, 7); thus, Treg are currently defined as a subset of CD4 lymphocytes with the surface marker profile CD4+CD25+CD127low and which express the intracellular transcription factor FoxP3.”
BackgroundLe, N. T., & Chao, N. J. A. (2006) · Bone Marrow Transplantation · doi:10.1038/sj.bmt.1705529 · Cited by 59
Regulatory T cells as a potent target for controlling bone loss
Yuan, F., Li, X., Lü, W., Xu, R., Zhao, Y., Li, C.-W., Li, J., & Chen, F. (2010) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2010.09.120 · Cited by 61
Manipulation of regulatory T-cell number and function with CD28-specific monoclonal antibodies
Hünig, T. (2007) · Advances in Immunology · doi:10.1016/s0065-2776(07)95004-x · Cited by 57
Phillips, B. E., Garciafigueroa, Y., Engman, C., Trucco, M., & Giannoukakis, N. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00148 · Cited by 58
Regulatory T Cell Dysfunction in Autoimmune Diseases
Honing, D. Y., Luiten, R. M., & Matos, T. R. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25137171 · Cited by 65
“To refine the characterization of human Tregs, recent research has emphasized the importance of low levels of CD127 (IL-7 receptor α -chain) combined with high CD25 expression to isolate FoxP3 expressing CD4 + T cells effectively (Table 2) [43,44].”
BackgroundEffects of Natalizumab Treatment on Foxp3+ T Regulatory Cells
Stenner, M., Waschbisch, A., Buck, D., Doerck, S., Einsele, H., Toyka, K. V., & Wiendl, H. (2008) · PLoS ONE · doi:10.1371/journal.pone.0003319 · Cited by 57
“However, the additional staining for the recently described marker CD127 (IL-7 receptor) distinguishing Tregs from non-regulatory cells [28,29] and gating on the CD4+CD25CD127 population helped to consistently isolate highly pure (.”
The cellular immune system in the post-myocardial infarction repair process
Latet, S. C., Hoymans, V. Y., Herck, P. L. V., & Vrints, C. J. (2014) · International Journal of Cardiology · doi:10.1016/j.ijcard.2014.11.006 · Cited by 57
HIV-specific regulatory T cells are associated with higher CD4 cell counts in primary infection
Kared, H., Lelièvre, J., Donkova-Petrini, V., Aouba, A., Melica, G., Balbo, M., Weiss, L., & Lévy, Y. (2008) · AIDS · doi:10.1097/qad.0b013e328319edc0 · Cited by 57
“Although no specific markers have been described for characterization of human Treg, the expression of high levels of CD25 and low density of CD127 molecules has been correlated with immunosuppressive Treg activity in humans [30].”
Induction of transplantation tolerance through regulatory cells: from mice to men
Ferrer, I. R., Hester, J., Bushell, A., & Wood, K. J. (2014) · Immunological Reviews · doi:10.1111/imr.12158 · Cited by 58
“The observation that IL-7 receptor a-chain (CD127) expression inversely correlates with FOXP3 expression and regulatory function of human Tregs allowed for the refinement of human Treg phenotype as CD127 CD25 CD4 T cells (9, 10).”
BackgroundRegulatory and Pathogenic Mechanisms in Human Autoimmune Myasthenia Gravis
Panse, R. L., Cizeron‐Clairac, G., Cuvelier, M., Truffault, F., Bismuth, J., Nancy, P., de Rosbo, N. D., & Berrih-Aknin, S. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1405.019 · Cited by 61
Immunological determinants of the outcomes from primary hepatitis C infection
Post, J. J., Ratnarajah, S., & Lloyd, A. R. (2008) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-008-8270-4 · Cited by 58
Human CD4 + HLA‐G + regulatory T cells are potent suppressors of graft‐versus‐host disease in vivo
Pankratz, S., Bittner, S., Herrmann, A. M., Schuhmann, M. K., Ruck, T., Meuth, S. G., & Wiendl, H. (2014) · The FASEB Journal · doi:10.1096/fj.14-251074 · Cited by 58
“Intranuclear FoxP3 staining was performed with an intracellular fixation and permeabilization kit (eBiosciences) modified to manufacturer’s protocol with FoxP3-Alexa Fluor 488 (clone 259D; BioLegend) mAB.”
BackgroundInfluentialScally, S. W., Law, S. C., Ting, Y. T., van Heemst, J., Sokolove, J. B., Deutsch, A. J., Clemens, E. B., Moustakas, A. K., Papadopoulos, G. K., van der Woude, D., et al. (2017) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2017-211300 · Cited by 59
Edwards, E. S. J., Bosco, J. J., Aui, P. M., Stirling, R. G., Cameron, P. U., Chatelier, J., Hore‐Lacy, F., O’Hehir, R. E., & van Zelm, M. C. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02593 · Cited by 53
“Finally, an 11-color Th-subset tube was designed based on our previous work (66) with the objective to use membrane markers to distinguish Treg (67, 68), helper T-cell subsets (Th) (69, 70), and Tfh (71, 72), and their subsets (73) (Supplementary Figure 4 and Supplementary Tables 1–3).”
MethodXydia, M., Rahbari, R., Ruggiero, E., Macaulay, I. C., Tarabichi, M., Lohmayer, R., Wilkening, S., Michels, T., Brown, D. V., Vanuytven, S., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-21297-y · Cited by 59
Sewgobind, V. D. K. D., Kho, M. M. L., van der Laan, L. J. W., Hendrikx, T. K., van Dam, T., Tilanus, H. W., IJzermans, J. N. M., Weimar, W., & Baan, C. C. (2009) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfn778 · Cited by 59
“Other molecular mechanisms of immunoregulatory CD4+ T cell-mediated suppression are through the secretion of IL-10 and TGF-β and via killing of the Teff directly by cytolysis [17,18].”
BackgroundRichardson, N., Wootton, G. E., Bozward, A. G., & Oo, Y. H. (2022) · Seminars in Immunopathology · doi:10.1007/s00281-022-00940-w · Cited by 58
“[25, 26] and expression of IL-7 receptor (CD127) inversely correlates with Foxp3 in CD4+CD25high + T cells [27, 28].”
BackgroundDrennan, S., Stafford, N. D., Greenman, J., & Green, V. L. (2013) · Immunology · doi:10.1111/imm.12144 · Cited by 56
Zhao, Y., Lutalo, P., Thomas, J. E., Sangle, S. R., Choong, L., Tyler, J. R., Tree, T. I. M., Spencer, J., & D’Cruz, D. P. (2013) · Rheumatology · doi:10.1093/rheumatology/ket406 · Cited by 58
Sprangers, B., DeWolf, S., Savage, T. M., Morokata, T., Obradović, A., LoCascio, S. A., Shonts, B. A., Zuber, J., Lau, S. P., Shah, R., et al. (2017) · American Journal of Transplantation · doi:10.1111/ajt.14251 · Cited by 58
“Tregs express high levels of CD25 (15, 16) and lack cell surface CD127 (IL-7 receptor a-chain) expression (17, 18).”
Staser, K. W., Eades, W. C., Choi, J., Karpova, D., & DiPersio, J. F. (2017) · Cytometry Part A · doi:10.1002/cyto.a.23303 · Cited by 56
“Of note, HLADR and CD38 expression identifies T cell activation status within any subset (10), with an example shown for all CD41 cells.”
BackgroundInfluentialCD70 expression determines the therapeutic efficacy of expanded human regulatory T cells
Hornero, R. A., Georgiadis, C., Peng, H., Trzupek, D., He, L.-Z., Qasim, W., Todd, J. A., Ferreira, R. C., Wood, K. J., Issa, F., et al. (2020) · Communications Biology · doi:10.1038/s42003-020-1097-8 · Cited by 61
Assessing theIn VitroSuppressive Capacity of Regulatory T Cells
Brusko, T. M., Hulme, M. A., Myhr, C. B., Haller, M. J., & Atkinson, M. A. (2007) · Immunological Investigations · doi:10.1080/08820130701790368 · Cited by 56
Targeting regulatory T cells for immunotherapy in melanoma
Huang, L., Guo, Y., Liu, S., Wang, H., Zhu, J., Ou, L., & Xu, X. (2021) · Molecular Biomedicine · doi:10.1186/s43556-021-00038-z · Cited by 57
“It has been suggested that CD4CD25T cells can differentiate into CD127 Tregs and CD127 conventional Th cells [19, 20].”
BackgroundSignificantly reduced regulatory T cell population in patients with untreated multiple myeloma
Gupta, R., Ganesan, P., Hakim, M., Verma, R. K., Sharma, A., & Kumar, L. (2010) · Leukemia Research · doi:10.1016/j.leukres.2010.11.010 · Cited by 55
Simonetta, F., Lécuroux, C., Girault, I., Goujard, C., Sinet, M., Lambotte, O., Venet, A., & Bourgeois, C. (2012) · The Journal of Infectious Diseases · doi:10.1093/infdis/jis235 · Cited by 55
CD4+FOXP3+ Regulatory T-Cell Subsets in Human Immunodeficiency Virus Infection
Simonetta, F., & Bourgeois, C. (2013) · Frontiers in Immunology · doi:10.3389/fimmu.2013.00215 · Cited by 57
Ruiter, B., Smith, N. P., Monian, B., Tu, A. A., Fleming, E. S., Virkud, Y. V., Patil, S. U., Whittaker, C. A., Love, J. C., & Shreffler, W. G. (2019) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2019.09.033 · Cited by 55
Severson, C., & Hafler, D. A. (2009) · Results and problems in cell differentiation · doi:10.1007/400_2009_12 · Cited by 56
Deak, L. C., Vallotton, L., Ciuffreda, D., Venetz, J.-P., Garcia, M., Hadaya, K., Bühler, L. H., Rotman, S., Pascual, M. A., & Pantaleo, G. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20062120 · Cited by 55
“On the basis of the present results and of recent studies (15, 17), we then analyzed the correlation between IL-7Rα and FOXP3 expression in CD4+CD25+ T cells in stable transplant recipients.”
BackgroundResultInfluentialAdvances in Engineering Cells for Cancer Immunotherapy
Xu, X., Li, T., Shen, S., Wang, J., Abdou, P., Gu, Z., & Mo, R. (2019) · Theranostics · doi:10.7150/thno.38583 · Cited by 53
“6 TCRs result in phosphorylation of immunoreceptor tyrosine-based activation motifs (ITAMs), and therefore activate intracellular signaling in the T cells and release of cytokines, such as interferon-γ (IFN-γ)/interleukin-2 (IL-2) and cytotoxic proteins, such as perforin/granzyme [61, 64, 65].”
BackgroundVergati, M., Cereda, V., Madan, R. A., Gulley, J. L., Huen, N. Y. M., Rogers, C. J., Hance, K. W., Arlen, P. M., Schlom, J., & Tsang, K. Y. (2010) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-010-0927-9 · Cited by 54
Lemoine, F. M. (2009) · International Journal of Oncology · doi:10.3892/ijo_00000368 · Cited by 54
“nTregs are known to be CD3+CD4+ cells expressing high levels of CD25 (CD25hi), the transcription factor Foxp3, and low levels of CD127 (CD127low/-) (42,43).”
BackgroundCD4 +CD25 +Foxp3 regulatory T cells and vascular dysfunction in hypertension
Kassan, M., Wecker, A., Kadowitz, P. J., Trebak, M., & Matrougui, K. (2013) · Journal of Hypertension · doi:10.1097/hjh.0b013e328362feb7 · Cited by 55
“Furthermore, cells separated based only on CD4 þ and CD127 expression showed comparable suppressive capabilities to CD4 CD25 þ Tregs [43].”
BackgroundInfluentialZhang, W., Wang, J., Shu, Y., Tang, T., Zhu, Z., Xia, N., Nie, S., Liu, J., Zhou, S., Li, J., et al. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.382978 · Cited by 55
Zhang, H. H., Song, K., Rabin, R. L., Hill, B. J., Perfetto, S. P., Roederer, M., Douek, D. C., Siegel, R. M., & Farber, J. M. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0904156 · Cited by 55
Benito, M., García-Carmona, Y., Balsa, A., de Ayala, C. P., Cobo‐Ibáñez, T., Martín-Mola, E., & Miranda‐Carús, M. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0900007 · Cited by 54
“1, A and B), further confirming the previously described characteristic phenotype of both populations (32, 33).”
Karlsson, I., Malleret, B., Brochard, P., Delache, B., Calvo, J., Grand, R. L., & Vaslin, B. (2007) · Journal of Virology · doi:10.1128/jvi.01466-07 · Cited by 54
“Low surface expression of CD127 in combination with CD25 has recently been shown to be an accurate means of identifying human regulatory T cells (40, 58).”
BackgroundPartial dysfunction of Treg activation in sickle cell disease
Vingert, B., Tamagne, M., Desmarets, M., Pakdaman, S., Elayeb, R., Habibi, A., Bernaudin, F., Galactéros, F., Bierling, P., Pirenne, F., et al. (2013) · American Journal of Hematology · doi:10.1002/ajh.23629 · Cited by 53
“Results Treg frequency and subpopulations in transfused SCD patients We identified Treg as having a CD31CD41CD25hiCD127loFoxp31 phenotype (Supporting Information) [16,17].”
ResultInfluentialPiper, K. P., Karanth, M., McLarnon, A., Kalk, E., Khan, N., Murray, J., Pratt, G., & Moss, P. A. H. (2011) · Clinical & Experimental Immunology · doi:10.1111/j.1365-2249.2011.04466.x · Cited by 53
Flanagan, K. L., Halliday, A., Burl, S., Landgraf, K., Jagne, Y. J., Noho‐Konteh, F., Townend, J., Miles, D. J. C., van der Sande, M. A. B., Whittle, H. C., et al. (2009) · European Journal of Immunology · doi:10.1002/eji.200939638 · Cited by 53
Functional dynamics of Foxp3+ regulatory T cells in mice and humans
Dhuban, K. B., Kornete, M., Mason, E. S., & Piccirillo, C. A. (2014) · Immunological Reviews · doi:10.1111/imr.12168 · Cited by 54
“and others (163, 165) have suggested that the lack of IL-7 receptor a chain (CD127) expression on CD4 cells can be used to identify and sort FOXP3 Treg cells from CD25 and CD25 cells, thus capturing the majority of FOXP3 cells.”
BackgroundGPA33: A Marker to Identify Stable Human Regulatory T Cells
Opstelten, R., de Kivit, S., Slot, M. C., van den Biggelaar, M., Iwaszkiewicz‐Grześ, D., Gliwiński, M., Scott, A. M., Blom, B., Trzonkowski, P., Borst, J. G., et al. (2020) · The Journal of Immunology · doi:10.4049/jimmunol.1901250 · Cited by 54
Lim, H. W., & Kim, C. H. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.11.7448 · Cited by 54
Baecher‐Allan, C., Costantino, C. M., Cvetanovich, G. L., Ashley, C. W., Bériou, G., Dominguez‐Villar, M., & Hafler, D. A. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1002502 · Cited by 53
“It is clear that low levels of CD127 (IL-7Ra–chain) expression identify CD4CD25 cells that express high levels of FOXP3 and exhibit in vitro suppressor activity (13, 16), and yet the data in these two seminal reports also demonstrated that a small population of *Division of Molecular Immunology, Center for Neurologic…”
BackgroundCD26: A negative selection marker for human Treg cells
Salgado, F. J., Pérez, A. C., Villanueva, N. M., Lamas, O., Arias, P., & Nogueira, M. (2012) · Cytometry Part A · doi:10.1002/cyto.a.22117 · Cited by 52
“CD127 is another protein whose levels inversely correlate with FoxP3 expression in Treg lymphocytes (17,18).”
BackgroundInflammation‐independent defective early B cell tolerance checkpoints in rheumatoid arthritis
Menard, L. C., Samuels, J., Ng, Y.-S., & Meffre, E. (2010) · Arthritis & Rheumatism · doi:10.1002/art.30164 · Cited by 52
“CD4 CD25CD127 CD62L Treg cells (13,14) (Figure 2).”
Novel Gamma-Chain Cytokines as Candidate Immune Modulators in Immune Therapies for Cancer
Fewkes, N. M., & Mackall, C. L. (2010) · The Cancer Journal · doi:10.1097/ppo.0b013e3181eacbc4 · Cited by 54
Broux, B., Hellings, N., Venken, K., Rummens, J., Hensen, K., Wijmeersch, B. V., & Stinissen, P. (2010) · Genes and Immunity · doi:10.1038/gene.2009.106 · Cited by 53
STAT Transcription Factors in T Cell Control of Health and Disease
Goswami, R., & Kaplan, M. H. (2016) · International review of cytology · doi:10.1016/bs.ircmb.2016.09.012 · Cited by 52
Salman, J., Ius, F., Knoefel, A.-K., Sommer, W., Siemeni, T., Kuehn, C., Tudorache, I., Avsar, M., Nakagiri, T., Preißler, G., et al. (2016) · American Journal of Transplantation · doi:10.1111/ajt.14148 · Cited by 52
“22 Postoperative pulsed steroid therapy 13 (12) 4 (13) 0.”
BackgroundInfluentialBuckner, J. H., & Ziegler, S. F. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1443.014 · Cited by 52
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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