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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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The role of T regulatory cells in human sepsis
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Patients with posttraumatic stress disorder exhibit an altered phenotype of regulatory T cells
Jergović, M., Bendelja, K., Vidović, A., Savić, A., Vojvoda, V., Aberle, N., Rabatić, S., Jovanovic, T., & Sabioncello, A. (2014) · Allergy, Asthma & Clinical Immunology · doi:10.1186/1710-1492-10-43 · Cited by 49
“T cells [12] and frequency of CD127 expressing cells within the FOXP3 population correlates with poor Treg function [13].”
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“The blood SAMHD1 CD4 T-cell compartment decrease is restricted to T-helper 17 cells As differential susceptibility to HIV-1 infection has been described for CD4þ T-cell subsets [16–19], we further examined the expression of SAMHD1 in Th1 (CD45ROþCXCR3þCCR4 CCR6 ), Th2 (CD45ROþCXCR3 CCR4þCCR6 ), Th17 (CD45 ROþCXCR3 CCR…”
BackgroundSelf-citationCancer immunotherapy with T-cell targeting cytokines: IL-2 and IL-7
Kim, J., Lee, K.-J., & Lee, S. (2021) · BMB Reports · doi:10.5483/bmbrep.2021.54.1.257 · Cited by 52
“The high-affinity trimeric IL-2R is predominantly expressed on immunosuppressive CD4+Foxp3+ regulatory T (TREG) cells via constitutive expression of IL-2R at high levels, whereas other T subsets transiently upregulate IL-2R after activation following T-cell receptor (TCR) stimulation (10).”
BackgroundInfluentialWeiss, L., Piketty, C., Assoumou, L., Didier, C., Caccavelli, L., Donkova-Petrini, V., Lévy, Y., Girard, P., Burgard, M., Viard, J., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0011659 · Cited by 51
“irrespective of their level of CD25 expression [24,25,26].”
Regulation Generation: The Suppressive Functions of Human Regulatory T Cells
Goodman, W. A., Cooper, K. D., & McCormick, T. S. (2012) · Critical Reviews in Immunology · doi:10.1615/critrevimmunol.v32.i1.40 · Cited by 52
Onoe, T., Kalscheuer, H., Danzl, N. M., Chittenden, M., Zhao, G., Yang, Y., & Sykes, M. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1100394 · Cited by 52
“Expression of a-chains of IL-2 and IL-7 receptors (CD25 and CD127, respectively) discriminates between human Tregs and activated T cells (29), and CD127 expression inversely correlates with FOXP3 expression and suppressive function of human Tregs (30).”
BackgroundInfluence of Short-Term Glucocorticoid Therapy on Regulatory T Cells In Vivo
Sbiera, S., Dexneit, T., Reichardt, S. D., Michel, K. D., van den Brandt, J., Schmull, S., Kraus, L., Beyer, M., Mlynski, R. A., Wortmann, S., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0024345 · Cited by 51
“However, this change was only significant when using FOXP3+, CD127low and CTLA4+ as definition of Treg cells but not AITR +. Similarly, the frequency of FOXP3+ Treg cells within the CD4 + T cell population decreased slightly, whereas the relative number of CD127low Treg cells increased and the one of AITR+ and CTLA4+…”
MethodInfluentialLiver X receptor activation promotes differentiation of regulatory T cells
Herold, M. V. B., Breuer, J., Hucke, S., Knolle, P. A., Schwab, N., Wiendl, H., & Klotz, L. (2017) · PLoS ONE · doi:10.1371/journal.pone.0184985 · Cited by 54
The role of regulatory T cells in graft-versus-host disease management
Whangbo, J., Antin, J. H., & Koreth, J. (2019) · Expert Review of Hematology · doi:10.1080/17474086.2020.1709436 · Cited by 51
“expression of CD127, the α-chain of the interleukin-7 receptor [15,16].”
BackgroundIsolation of human antigen‐specific regulatory T cells with high suppressive function
Noyan, F., Lee, Y., Zimmermann, K., Hardtke‐Wolenski, M., Taubert, R., Warnecke, G., Knoefel, A.-K., Schulde, E., Olek, S., Manns, M. P., et al. (2014) · European Journal of Immunology · doi:10.1002/eji.201344381 · Cited by 50
Xu, W., Zhang, A., Ren, M., Zhang, X.-D., Wang, F., Xu, X., Li, Q., Wang, J., Din, B.-S., Wu, Y., et al. (2012) · Journal of Clinical Immunology · doi:10.1007/s10875-012-9685-0 · Cited by 50
“CD127 cells represent recently activated CD4 effector T cells, and a lack of CD127 expression, when combined with CD25, that is, CD4CD25CD127/ T cells,also have been identified as Tregs in some researches [19].”
BackgroundRegulatory T Cells and Allergic Disease
Nouri‐Aria, K. T., & Durham, S. R. (2008) · Inflammation & Allergy - Drug Targets · doi:10.2174/187152808786848405 · Cited by 50
“Freshly isolated CD4 + CD25 + T cells were anergic, as they failed to proliferate after T cell receptor (TCR) stimulation in vitro, whereas the addition of exogenous IL-2 reversed and generated potent T cell responses [15, 23-25].”
BackgroundEffect of chorioamnionitis on regulatory T cells in moderate/late preterm neonates
Rueda, C. M., Wells, C. B., Gisslen, T. A., Jobe, A. H., Kallapur, S. G., & Chougnet, C. A. (2014) · Human Immunology · doi:10.1016/j.humimm.2014.10.016 · Cited by 50
“neonates, having similar percentages of Treg when these cells were defined with the combination of these molecules (CD25Foxp3; CD25CD127 , Foxp3CD127) [30].”
BackgroundRegulatory T Cell Responses to High-Dose Methylprednisolone in Active Systemic Lupus Erythematosus
Mathian, A., Jouenne, R., Chader, D., Aubart, F. C., Haroche, J., Fadlallah, J., Claër, L., Musset, L., Gorochov, G., Amoura, Z., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0143689 · Cited by 50
“PBMCs were surface-stained with monoclonal antibodies: PerCP-conjugated-anti-CD4, APC-H7-conjugated-anti-CD45RA, BV450-conjugated-anti CD127, PeCy7-conjugated-anti CD25 (all from BD bioscience).”
Targeting Aurora kinase A and JAK2 prevents GVHD while maintaining T reg and antitumor CTL function
Betts, B. C., Veerapathran, A., Pidala, J., Yang, H., Horna, P., Walton, K., Cubitt, C. L., Gunawan, S., Lawrence, H. R., Lawrence, N. J., et al. (2017) · Science Translational Medicine · doi:10.1126/scitranslmed.aai8269 · Cited by 50
“Activated CD4 Tconv were identified as coexpressing CD25 and CD127 (32–34), and the latter assisted in excluding Tregs from the analysis (35, 36).”
BackgroundMethodFollicular Regulatory T Cells Are Highly Permissive to R5-Tropic HIV-1
Miller, S. M., Miles, B., Guo, K., Folkvord, J. M., Meditz, A. L., McCarter, M. D., Levy, D. N., MaWhinney, S., Santiago, M. L., & Connick, E. (2017) · Journal of Virology · doi:10.1128/jvi.00430-17 · Cited by 50
Terry, L. V., & Oo, Y. H. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.565518 · Cited by 51
“Further to this, expression of the IL-7 receptor, CD127, correlated inversely with Foxp3 expression and Treg cell suppressive function; hence Treg cells are currently defined as CD4+CD25highCD127lowFoxp3+ cells (7, 8).”
BackgroundDemirkıran, A., Bosma, B. M., Kok, A., Baan, C. C., Metselaar, H. J., IJzermans, J. N. M., Tilanus, H. W., Kwekkeboom, J., & van der Laan, L. J. W. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.10.6066 · Cited by 50
“Recently, the absence of the IL-7R CD127 expression has been suggested as a discriminating factor of Foxp3 Treg (30, 31).”
BackgroundThe Time is Crucial for Ex Vivo Expansion of T Regulatory Cells for Therapy
Marek-Trzonkowska, N. M., Bieniaszewska, M., Krzystyniak, A., Juścińska, J., Myśliwska, J. M., Witkowski, P., Hellmann, A. R., & Trzonkowski, P. (2011) · Cell Transplantation · doi:10.3727/096368911x566217 · Cited by 49
Impaired inhibitory function of circulating CD4+CD25+ regulatory T cells in alopecia areata
Shin, B. S., Furuhashi, T., Nakamura, M., Torii, K., & Morita, A. (2013) · Journal of Dermatological Science · doi:10.1016/j.jdermsci.2013.01.006 · Cited by 49
Proietti, E., Moschella, F., Capone, I., & Belardelli, F. (2011) · Molecular Oncology · doi:10.1016/j.molonc.2011.11.005 · Cited by 50
“Considering that the g chain of the IL-7 receptor is expressed only at low levels in regulatory T cells (Seddiki et al., 2006), all these observations suggest that the CTXinduced homeostatic cytokinesmay act synergistically in promoting the proliferation/activation of effector/memory T cells…”
BackgroundAbdulahad, W. H., Boots, A. M. H., & Kallenberg, C. G. M. (2010) · Rheumatology · doi:10.1093/rheumatology/keq328 · Cited by 49
Bikker, A., van Vliet-Moret, F. M., Kruize, A. A., Bijlsma, J. W. J., Lafeber, F. P. J. G., & van Roon, J. A. G. (2012) · Lara D. Veeken · doi:10.1093/rheumatology/ker448 · Cited by 49
Ianni, M. D., Falzetti, F., Carotti, A., Terenzi, A., Papa, B. D., Perruccio, K., Ruggeri, L., Sportoletti, P., Rosati, E., Marconi, P., et al. (2011) · Best Practice & Research Clinical Haematology · doi:10.1016/j.beha.2011.05.005 · Cited by 50
Silver nanoparticles for the detection of cell surface antigens in mass cytometry
Schulz, A. R., Stanislawiak, S., Baumgart, S., Grützkau, A., & Mei, H. E. (2016) · Cytometry Part A · doi:10.1002/cyto.a.22904 · Cited by 49
CD4+CD25+ T Regulatory Cells in Transplantation Tolerance
Hall, B. M. (2016) · Transplantation · doi:10.1097/tp.0000000000001436 · Cited by 49
Landwehr-Kenzel, S., Müller‐Jensen, L., Kuehl, J.-S., Abou‐El‐Enein, M., Hoffmann, H., Muench, S., Kaiser, D., Roemhild, A., von Bernuth, H., Völler, M., et al. (2022) · Molecular Therapy · doi:10.1016/j.ymthe.2022.02.025 · Cited by 48
Alterations in Regulatory T Cell Subpopulations Seen in Preterm Infants
Luciano, A. A., Arbona, I. M., Ruiz, R., Llorens-Bonilla, B. J., Martinez-Lopez, D. G., Funderburg, N., & Dorsey, M. J. (2014) · PLoS ONE · doi:10.1371/journal.pone.0095867 · Cited by 50
“Treg percentages and gestational age Tregs were identified by size, granularity (Figure 1A), and coexpression of CD3 and CD4 (Figure 1B), CD25 and FOXP3 (Figure 1C) and CD45RA (Figure 1D).”
BackgroundInfluentialRabe, H., Nordström, I., Andersson, K. M., Lundell, A., & Rudin, A. (2013) · Immunology · doi:10.1111/imm.12209 · Cited by 48
Interleukin-7 Influences FOXP3+CD4+ Regulatory T Cells Peripheral Homeostasis
Simonetta, F., Gestermann, N., Martinet, K. Z., Boniotto, M., Tissières, P., Seddon, B. P., & Bourgeois, C. (2012) · PLoS ONE · doi:10.1371/journal.pone.0036596 · Cited by 48
“The only important exception seems to be represented by CD4 FOXP3 Treg which have been reported to express low levels of the IL-7 receptor alpha chain (CD127) [21–23].”
BackgroundHorta, A., Nóbrega, C., Amorim-Machado, P., Coutinho-Teixeira, V., Barreira‐Silva, P., Boavida, S., Costa, P., Sarmento‐Castro, R., Castro, A. G., & Correia‐Neves, M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0057336 · Cited by 48
“More recently, it was shown that Tregs express low levels of CD127 (the IL-7Ra chain), and therefore this molecule is considered useful as an additional marker to identify this population [47,48,49,50].”
BackgroundLong-Term Effects of Alemtuzumab on Regulatory and Memory T-Cell Subsets in Kidney Transplantation
Macedo, C., Walters, J., Orkis, E. A., Isse, K., Elinoff, B. D., Fedorek, S., McMichael, J., Chalasani, G., Randhawa, P. S., Demetris, A. J., et al. (2012) · Transplantation · doi:10.1097/tp.0b013e318247a717 · Cited by 48
Expansion of regulatory GITR+CD25low/-CD4+ T cells in systemic lupus erythematosus patients
Nocentini, G., Alunno, A., Petrillo, M. G., Bistoni, O., Bartoloni, E., Caterbi, S., Ronchetti, S., Migliorati, G., Riccardi, C., & Gerli, R. (2014) · Arthritis Research & Therapy · doi:10.1186/s13075-014-0444-x · Cited by 48
“Other proteins are differentially expressed in Tregs and a number of different Treg subsets, characterized by one or more markers, have been described [23-27].”
BackgroundTheodoraki, M., Lorenz, K., Lotfi, R., Fürst, D., Tsamadou, C., Jaekle, S., Mytilineos, J., Brunner, C., Theodorakis, J., Hoffmann, T., et al. (2017) · Photodiagnosis and Photodynamic Therapy · doi:10.1016/j.pdpdt.2017.05.015 · Cited by 46
Cabral, J., Hanley, S. A., Gerlach, J. Q., O’Leary, N., Cunningham, S., Ritter, T., Ceredig, R. H., Joshi, L., & Griffin, M. D. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00987 · Cited by 47
“Regulatory T-cells (Treg) can be distinguished from conventional CD4+ T-cells (Tconv) by intracellular expression of the transcription factor FoxP3 (1) and, in humans, by a CD25highCD127low phenotype (2).”
BackgroundInfluentialMa, F., Li, S., Gao, X., Zhou, J., Zhu, X., Wang, D., Cai, Y., Li, F., Yang, Q., Gu, X., et al. (2019) · EBioMedicine · doi:10.1016/j.ebiom.2019.05.042 · Cited by 48
“Intriguingly, as in Th17 cells, CCR9+ IL-17+ Treg cells expressed higher levels of CCR6, CD161, IL-17, and CD127 compared to conventional Treg cells (Fig.”
BackgroundMethodInfluentialKim, J., Hope, C. M., Gantumur, N., Perkins, G. B., Stead, S. O., Yue, Z., Liu, X., Urigoitia-Asua, A., Kette, F. D., Penko, D., et al. (2020) · Advanced Functional Materials · doi:10.1002/adfm.202000544 · Cited by 48
Immunopathogenesis of IBD: insufficient suppressor function in the gut?
Huibregtse, I. L., van Lent, A. U., & van Deventer, S. J. H. (2006) · Gut · doi:10.1136/gut.2006.103523 · Cited by 50
Regulatory T Cells in HIV Infection: Can Immunotherapy Regulate the Regulator?
Jenabian, M.-A., Ancuța, P., Gilmore, N. J., & Routy, J. (2012) · Clinical and Developmental Immunology · doi:10.1155/2012/908314 · Cited by 50
“in 2006 demonstrated that, in addition to a CD25FoxP3high phenotype, Tregs can be further identified by their low expression of CD127 (the alpha chain of the IL-7 receptor) [9, 10].”
BackgroundRegulatory T cells participate in the recovery of ischemic stroke patients
Santamaría-Cadavid, M., Castro, E. R., Rodríguez‐Yáñez, M., Arias-Rivas, S., López‐Dequidt, I., Pérez‐Mato, M., Rodríguez-Pérez, M., López-Loureiro, I., Hervella, P., Campos, F., et al. (2020) · BMC Neurology · doi:10.1186/s12883-020-01648-w · Cited by 47
The Role of Regulatory T Cells in the Pathogenesis of Sepsis and Its Clinical Implication
Jiang, L., Yao, Y.-M., & Sheng, Z.-Y. (2012) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.2011.0080 · Cited by 47
Functional regulatory T cells and allergen immunotherapy
Rolland, J. M., Gardner, L. M., & O’Hehir, R. E. (2010) · Current Opinion in Allergy and Clinical Immunology · doi:10.1097/aci.0b013e32833ff2b2 · Cited by 47
Different Immunosuppressive Combinations on T-Cell Regulation in Renal Transplant Recipients
Fourtounas, C., Dousdampanis, P., Sakellaraki, P., Rodi, M., Georgakopoulos, T., Vlachojannis, J. G., & Mouzaki, Α. (2010) · American Journal of Nephrology · doi:10.1159/000313940 · Cited by 47
“However, a recent study has associated increased blood levels of CD4+CD25 high FoxP3+ Tregs with dermatological malignancies [ ,”
BackgroundDifferentiation of human thymic regulatory T cells at the double positive stage
Nunes‐Cabaço, H., Caramalho, Í., Sepúlveda, N., & Sousa, A. E. (2011) · European Journal of Immunology · doi:10.1002/eji.201141614 · Cited by 47
Cao, T., Soto, A., Zhou, W., Wang, W., Eck, S., Walker, M., Harriman, G. R., & Li, L. Y. (2009) · Cellular Immunology · doi:10.1016/j.cellimm.2009.03.013 · Cited by 47
“First, enhance the purity of the starting Treg population by using CD4+CD25+CD127 Tregs, however this may require the cell sorter to meet GMP compliance for clinical use, which will be costly and time consuming [23,24].”
BackgrounddeLeeuw, R. J., Kroeger, D. R., Kost, S. E. F., Chang, P.-P., Webb, J. R., & Nelson, B. H. (2014) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-14-0146 · Cited by 48
Liberal, R., Grant, C. R., Yüksel, M., Graham, J. J., Kalbasi, A., Ma, Y., Heneghan, M. A., Mieli‐Vergani, G., Vergani, D., & Longhi, M. S. (2017) · Hepatology · doi:10.1002/hep.29307 · Cited by 47
“(1,2) Abbreviations: [A], patient with active disease; AIH, autoimmune hepatitis; AISC, autoimmune sclerosing cholangitis; FOXP3, forkhead box P3; HS, healthy subjects; IFNc, interferon gamma; IL, interleukin; MMF, mycophenolate mofetil; PBMC, peripheral blood mononuclear cell; PE, phycoerythrin; pSTAT5, phospho signa…”
InfluentialPillai, V., & Karandikar, N. J. (2007) · Immunology Letters · doi:10.1016/j.imlet.2007.08.012 · Cited by 48
“Liu W, Putnam AL, Xu-Yu Z, Szot GL, Lee MR, Zhu S, et al. CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells.”
BackgroundInfluentialRegulatory T cells in autoimmune kidney diseases and transplantation
Mikami, N., & Sakaguchi, S. (2023) · Nature Reviews Nephrology · doi:10.1038/s41581-023-00733-w · Cited by 46
Schlieer, U., Streitz, M., & Sawitzki, B. (2011) · Current Opinion in Organ Transplantation · doi:10.1097/mot.0b013e32834ee69f · Cited by 46
“Accordingly, the constitutive high expression of CD25 but low expression of CD127 has been used to discriminate them from activated effector T cells [18].”
BackgroundYounas, M., Hüe, S., Lacabaratz, C., Guguin, A., Wiedemann, A., Surénaud, M., Beq, S., Croughs, T., Lelièvre, J., & Lévy, Y. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1203547 · Cited by 46
“Cells were washed, and three living Treg subpopulations (i.e., naive, activated, and memory Tregs) were defined on the basis of CD45RA/CD127/CD25 expression.”
BackgroundInfluentialThe proportion of peripheral regulatory T cells in patients with Multiple Sclerosis: A meta-analysis
Li, Y., Zhang, S., Ma, X., Xue, Y.-L., Gao, C., Li, X., & Xu, A.-D. (2018) · Multiple Sclerosis and Related Disorders · doi:10.1016/j.msard.2018.12.019 · Cited by 46
Julé, A. M., Hoyt, K. J., Wei, K., Gutiérrez‐Arcelus, M., Taylor, M. L., Ng, J., Lederer, J. A., Case, S., Chang, M. H., Cohen, E. M., et al. (2021) · JCI Insight · doi:10.1172/jci.insight.149185 · Cited by 44
“may actually contain activated, non-regulatory T cells (21, 50).”
Offerhaus, G. J. A., Schipper, M. E. I., Lazenby, A. J., Montgomery, E., Morsink, F. H. M., Bende, R. J., Musler, A. R., van Lier, R. A. W., & van Noesel, C. J. M. (2007) · Immunology Letters · doi:10.1016/j.imlet.2007.08.010 · Cited by 46
Specific recruitment of regulatory T cells into the CSF in lymphomatous and carcinomatous meningitis
Haas, J., Schopp, L., Storch-Hagenlocher, B., Fritzsching, B., Jacobi, C., Milkova, L., Fritz, B., Schwarz, A., Suri‐Payer, E., Hensel, M., et al. (2007) · Blood · doi:10.1182/blood-2007-08-104877 · Cited by 47
Why T Cells of Thymic Versus Extrathymic Origin Are Functionally Different
Blais, M., Brochu, S., Giroux, M., Bélanger, M.-P., Dulude, G., Sékaly, R., & Perreault, C. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.4.2299 · Cited by 46
“Recent studies showing that human and mouse FoxP3 Treg cells express low levels of IL-7R provide suggestive evidence that FoxP3 may repress transcription of IL-7R (40, 41).”
BackgroundWithin-woman change in regulatory T cells from pregnancy to the postpartum period
Wegienka, G., Havstad, S. L., Bobbitt, K. R., Woodcroft, K. J., Zoratti, E. M., Ownby, D. R., & Johnson, C. C. (2010) · Journal of Reproductive Immunology · doi:10.1016/j.jri.2010.06.157 · Cited by 45
“Lymphocytes that were D4+CD25+FOXP3+CD127− were considered to be Treg ells (Liu et al., 2006; Seddiki et al., 2006; Santner-Nanan t al., 2008).”
BackgroundRegulatory T cell expression of CLA or α4β7 and skin or gut acute GVHD outcomes
Engelhardt, B. G., Jagasia, M., Savani, B. N., Bratcher, N. L., Greer, J. P., Jiang, A., Kassim, A. A., Lu, P., Schuening, F., Yoder, S. M., et al. (2010) · Bone Marrow Transplantation · doi:10.1038/bmt.2010.127 · Cited by 45
Sasson, S. C., Smith, S. A. B. C., Seddiki, N., Zaunders, J. J., Bryant, A. J., Koelsch, K. K., Weatherall, C. J., Munier, C. M. L., McGinley, C., Yeung, J. Y. K., et al. (2010) · Cytokine · doi:10.1016/j.cyto.2009.12.001 · Cited by 45
Self-citationChoi, Y. S., Lee, J., Lee, H. W., Chang, D.-Y., Sung, P. S., Jung, M. K., Park, J. Y., Kim, J. K., Lee, J. I., Park, H., et al. (2014) · Gut · doi:10.1136/gutjnl-2013-306213 · Cited by 46
Circulating lymphocyte subsets in different clinical situations after renal transplantation
van de Berg, P. J. E. J., Hoevenaars, E. C., Yong, S. L., der Pant, K. A. M. I. V. D., van Tellingen, A., Florquin, S., van Lier, R. A. W., Bemelman, F. J., & ten Berge, I. J. M. (2012) · Immunology · doi:10.1111/j.1365-2567.2012.03570.x · Cited by 45
Raghavan, S., Cao, D., Widhe, M., Roth, K., Herrath, J., Engström, M., Roncador, G., Banham, A. H., Trollmo, C., Catrina, A. I., et al. (2008) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2008.100768 · Cited by 45
“However, since FOXP3 is an intranuclear protein, viable cells cannot be isolated for functional assays. Extensive search for new markers that correlate with FOXP3 expression”
BackgroundRegulatory T Cells and Their Prognostic Relevance in Hematologic Malignancies
D'Arena, G. F., Vitale, C., Coscia, M., Festa, A., Minno, M. N. D. D., Feo, V. D., Caraglia, M., Calapai, G., Laurenti, L., Musto, P., et al. (2017) · Journal of Immunology Research · doi:10.1155/2017/1832968 · Cited by 45
Rallón, N. I., Lopez, M. J., Soriano, V., García‐Samaniego, J., Romero, M. G., Labarga, P., García‐Gascó, P., González‐Lahoz, J., & Benito, J. M. (2008) · Clinical & Experimental Immunology · doi:10.1111/j.1365-2249.2008.03797.x · Cited by 45
Mechanisms in allergic airway inflammation – lessons from studies in the mouse
Shum, B. O. V., Rolph, M. S., & Sewell, W. A. (2008) · Expert Reviews in Molecular Medicine · doi:10.1017/s1462399408000707 · Cited by 45
Emery, A., Moore, S. E., Turner, J. E., & Campbell, J. P. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.788113 · Cited by 49
Zhao, L., Yang, J., Wang, H.-P., & Liu, R.-Y. (2013) · Medical Oncology · doi:10.1007/s12032-013-0461-7 · Cited by 40
“For the analysis of Tregs, because the expression of FoxP3 protein and the CD127 phenotype is highly correlated within the CD4 CD25 population, we considered CD4 CD25 CD127 cells to be Tregs [10].”
BackgroundThe influence of HIV on CD127 expression and its potential implications for IL-7 therapy
Crawley, A. M., & Angel, J. B. (2012) · Seminars in Immunology · doi:10.1016/j.smim.2012.02.006 · Cited by 47
T regulatory cells and the control of alloimmunity: from characterisation to clinical application
Więckiewicz, J., Goto, R., & Wood, K. J. (2010) · Current Opinion in Immunology · doi:10.1016/j.coi.2010.08.011 · Cited by 44
The Role of FOXP3 in Regulating Immune Responses
Vent‐Schmidt, J., Han, J. M., MacDonald, K. G., & Levings, M. K. (2013) · International Reviews of Immunology · doi:10.3109/08830185.2013.811657 · Cited by 46
“In contrast, the IL-7Rα is specifically downregulated in human Tregs [64, 65].”
BackgroundDevelopment and Function of Effector Regulatory T Cells
Teh, P. P., Vasanthakumar, A., & Kallies, A. (2015) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2015.08.005 · Cited by 42
Usó, M., Jantus-Lewintre, E., Bremnes, R., Calabuig, S., Blasco, A., Pastor, E., Borredá, I., Molina-Pinelo, S., Paz-Ares, L., Guijarro, R., et al. (2016) · OncoTarget · doi:10.18632/oncotarget.10811 · Cited by 46
“On the other hand, regulatory T cells (Tregs) are a subtype of CD4+T cells with immunosuppressive properties that express high levels of CD25 and low levels of CD127 on their cell surface [17, 18].”
BackgroundPan, M., & Li, B. (2022) · eLife · doi:10.7554/elife.81952 · Cited by 42
“CD8- 01-XCL1 cluster expressed gene signatures of activated T cells, including Il7r ( Seddiki et al., 2006 ), ZFP36L2 ( Petkau et al., 2021 ), XCL1 ( Ordway et al., 2007 ), and CXCR6 ( Wang et al., 2021 ; Figure 3E ), as well as proliferation and mobility markers LDLRAD4 ( Liu et al., 2017 ) and…”
Haas, J., Korporal, M., Schwarz, A., Balint, B., & Wildemann, B. (2010) · European Journal of Immunology · doi:10.1002/eji.201041139 · Cited by 44
Péguillet, I., Milder, M., Louis, D., Vincent‐Salomon, A., Dorval, T., Piperno-Neumann, S., Scholl, S., & Lantz, O. J. (2014) · Cancer Research · doi:10.1158/0008-5472.can-13-2269 · Cited by 44
“Results Expansion of effector CD127 CD25 CD4þ T cells during chronic antigen stimulation In the course of monitoring Treg numbers in patients with various cancers using a CD25/CD127 staining of CD4þ T cells (26), we noticed the expansion of CD127 CD25 CD4þ T cells in peripheral blood lymphocytes (PBL; Fig.”
BackgroundVenken, K., Hellings, N., Hensen, K., Rummens, J., & Stinissen, P. (2010) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2010.05.025 · Cited by 43
“Recent reports have revealed that theα-chain of the IL-7R (CD127) is expressed at low levels on the surface of regulatory CD4CD25FOXP3 T cells (regulatory T cells, Tregs), while conventional CD4 T cells (Tconv) are CD127 (Liu et al., 2006; Seddiki et al., 2006).”
BackgroundMorales-Tirado, V. M., Wichlan, D., Leimig, T., Street, S. E. A., Kasow, K. A., & Riberdy, J. M. (2010) · Clinical Immunology · doi:10.1016/j.clim.2010.11.003 · Cited by 43
“These characteristics comprise a broad consensus phenotype for human nTregs, at least until a definitive lineage specification marker is elucidated [15; 16] Secondly, conventional cell cycle analysis evaluates DNA content by propidium iodide staining of fixed cells [17], precluding functional analysis of specific subs…”
BackgroundPorter, C. M., Horvath‐Arcidiacono, J. A., Singh, A. K., Horvath, K. A., Bloom, E. T., & Mohiuddin, M. M. (2007) · Xenotransplantation · doi:10.1111/j.1399-3089.2007.00416.x · Cited by 43
“This is similar to data shown for Treg cell populations in human peripheral blood, lymph node, and spleen [31,32].”
ResultLoiseau, C., Réquena, M., Mavigner, M., Cazabat, M., Carrère, N., Suc, B., Barange, K., Alric, L., Marchou, B., Massip, P., et al. (2016) · Mucosal Immunology · doi:10.1038/mi.2016.7 · Cited by 44
IL-2 promotes early Treg reconstitution after allogeneic hematopoietic cell transplantation
Betts, B. C., Pidala, J., Kim, J., Mishra, A., Nishihori, T., Perez, L. E., Ochoa-Bayona, J. L., Khimani, F., Walton, K., Bookout, R., et al. (2017) · Haematologica · doi:10.3324/haematol.2016.153072 · Cited by 43
Transcriptional network profile on synovial fluid T cells in psoriatic arthritis
Fiocco, U., Martini, V., Accordi, B., Caso, F., Costa, L., Oliviero, F., Scanu, A., Facco, M., Boso, D., Gatto, M., et al. (2015) · Clinical Rheumatology · doi:10.1007/s10067-015-3002-2 · Cited by 44
Regulatory T-Cell Modulation by Green Tea in Chronic Lymphocytic Leukemia
D'Arena, G. F., Simeon, V., Martino, L. D., Statuto, T., D’Auria, F., Volpe, S., Deaglio, S., Maidecchi, A., Mattoli, L., Mercati, V., et al. (2013) · International Journal of Immunopathology and Pharmacology · doi:10.1177/039463201302600111 · Cited by 43
“More recently, low expression ofthe IL-7 receptor (CD127) has been recognized as a further Treg marker (20-21).”
BackgroundCD4+ regulatory T cells in solid organ transplantation
Issa, F., & Wood, K. J. (2010) · Current Opinion in Organ Transplantation · doi:10.1097/mot.0b013e32834017ae · Cited by 44
Increased Regulatory T Cell Counts in HIV‐Infected Nonresponders to Hepatitis B Virus Vaccine
Balado, M. D. M. D. P., Leal, M., Méndez‐Lagares, G., Mata, R., López-Cortés, L. F., Viciana, P., & Pacheco, Y. M. (2010) · The Journal of Infectious Diseases · doi:10.1086/653707 · Cited by 43
“Although FoxP3 is the most unambiguous marker of Treg cells [19], recent studies indicate that Treg cells down-regulate the expression of the IL-7 receptor (CD127), and a high correlation was found between levels of CD4CD25FoxP3 and CD4CD25CD127 in healthy subjects [20].”
BackgroundDaFonseca, S., Niessl, J., Pouvreau, S., Wacleche, V. S., Gosselin, A., Cleret‐Buhot, A., Bernard, N. F., Tremblay, C. L., Jenabian, M.-A., Routy, J., et al. (2015) · Retrovirology · doi:10.1186/s12977-015-0164-6 · Cited by 45
“Suppressive Tregs exhibit a CD25CD127FoxP3 phenotype [74,75].”
Iyer, A. V., Pahar, B., Boudreaux, M. J., Wakamatsu, N., Roy, A. F., Chouljenko, V. N., Baghian, A., Apetrei, C., Marx, P. A., & Kousoulas, K. G. (2008) · Vaccine · doi:10.1016/j.vaccine.2008.11.087 · Cited by 42
“CD127, the ␣-chain of the IL7 receptor, in combination with CD25, the ␣-chain of the IL2 receptor, were used to define the relative abundance of T reg cells within the population of conventional T cells [76] .”
MethodChen, H. (2010) · International Journal of Oncology · doi:10.3892/ijo_00000561 · Cited by 42
“This allowed us to distinguish Treg cells from other activated CD4+ T cells in peripheral blood from HCC patients and control individuals (38,39).”
BackgroundLehé, C. L., Ghebeh, H., Al-Sulaiman, A., Qudaihi, G. A., Al‐Hussein, K., Almohareb, F. I., Chaudhri, N. A., Alsharif, F. Z., Alzahrani, H. A., Tbakhi, A., et al. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-0050 · Cited by 42
CD30 Discriminates Heat Shock Protein 60-Induced FOXP3+CD4+ T Cells with a Regulatory Phenotype
de Kleer, I., Vercoulen, Y., Klein, M., Meerding, J., Albani, S., van der Zee, R., Sawitzki, B., Hamann, A., Kuis, W., & Prakken, B. J. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0901901 · Cited by 42
Schiavinato, J. L. D. S., Haddad, R., Saldanha‐Araújo, F., Baiochi, J. F., Araújo, A. G., Scheucher, P. S., Covas, D. T., Zago, M. A., & Panepucci, R. A. (2017) · Scientific Reports · doi:10.1038/s41598-017-03456-8 · Cited by 42
3D printed lattices as an activation and expansion platform for T cell therapy
Delalat, B., Harding, F. J., Gundsambuu, B., De‐Juan‐Pardo, E. M., Wunner, F. M., Wille, M., Jasieniak, M., Malatesta, K. A. L., Griesser, H. J., Simula, A., et al. (2017) · Biomaterials · doi:10.1016/j.biomaterials.2017.05.009 · Cited by 43
Rattik, S., Engelbertsen, D., Wigren, M., Ljungcrantz, I., Östling, G., Persson, M., Fredrikson, G. N., Bengtsson, E., Nilsson, J. Å., & Björkbacka, H. (2018) · Diabetes and Vascular Disease Research · doi:10.1177/1479164118817942 · Cited by 41
Szalay, B., Vásárhelyi, B., Cseh, Á., Tulassay, T., Deák, M., Kovács, L., & Balog, A. (2013) · Clinical Rheumatology · doi:10.1007/s10067-013-2352-x · Cited by 42
“More recently, it has been shown that the absence of CD127 expression can be used as an alternative to the transcription factor FoxP3 [26], and it is also generally accepted that CD127 inversely correlates with FoxP3 in CD4+ cells [27].”
BackgroundRegulatory function of cytomegalovirus-specific CD4+CD27−CD28− T cells
Tovar-Salazar, A., Patterson‐Bartlett, J., Jesser, R. D., & Weinberg, A. (2009) · Virology · doi:10.1016/j.virol.2009.11.038 · Cited by 42
“Compared with the entire CMV-stimulated CD4+ T-cell population, higher proportions of CD4+CD27−CD28− TR expressed FoxP3, TGFβ, granzyme B, perforin, GITR and PD-1, lower proportions expressed CD127 and PD1-L and similar proportions expressed CD25, CTLA4, Fas-L and GITR-L.”
InfluentialKovacsovics-Bankowski, M., Chisholm, L., Vercellini, J., Tucker, C., Montler, R. D., Haley, D. P., Newell, P. H., Ma, J., Tseng, P. C., Wolf, R., et al. (2014) · Journal for ImmunoTherapy of Cancer · doi:10.1186/preaccept-2094627261309808 · Cited by 42
Gennaro, P. D., Gerlini, G., Urso, C., Sestini, S., Brandani, P., Pimpinelli, N., & Borgognoni, L. (2016) · Clinical & Experimental Metastasis · doi:10.1007/s10585-016-9814-x · Cited by 42
Engineered Treg cells: The heir to the throne of immunotherapy
Stucchi, A., Maspes, F., Montee-Rodrigues, E., & Fousteri, G. (2023) · Journal of Autoimmunity · doi:10.1016/j.jaut.2022.102986 · Cited by 43
Rodríguez‐Pinto, D., Navas, A., Blanco, V. M., Ramírez, L. G., Garcerant, D., Cruz, A. R., Craft, N. A., & Saravia, N. G. (2012) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0001627 · Cited by 40
“Lack of expression of CD127, expression of GITR, or expression of Foxp3 have also been described as Treg markers [34–37].”
Background
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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