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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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BackgroundT regulatory cells, the evolution of targeted immunotherapy
Nizar, S. A., Meyer, B., Galustian, C., Kumar, D., & Dalgleish, A. G. (2010) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2010.02.001 · Cited by 41
Cord Blood Derived CD4+CD25high T Cells Become Functional Regulatory T Cells upon Antigen Encounter
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Narsale, A. A., Moya, R., & Davies, J. D. (2018) · Clinical Immunology · doi:10.1016/j.clim.2018.01.003 · Cited by 41
“In addition, regulatory cells were identified by their high expression of CD25 and low expression of CD127 as described previously [24,25] using the BD Biosciences Treg cocktail that includes antibodies specific for CD4, CD127 and CD25 with CD3 and CD45RO.”
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Taubert, R., Pischke, S., Schlué, J., Wedemeyer, H. H., Noyan, F., Heim, A., Lehner, F., Barg‐Hock, H., Klempnauer, J. L., Olek, S., et al. (2012) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2012.04264.x · Cited by 40
Infiltration Profile of Regulatory T Cells in Osteoarthritis-Related Pain and Disability
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MethodInfluentialBetts, B., Angelo, E. S. S., Kennedy, M. G., & Young, J. W. (2011) · Blood · doi:10.1182/blood-2011-06-363390 · Cited by 38
Salcido-Ochoa, F., Tsang, J. Y., Tam, P. K. H., Falk, K., & Rötzschke, O. (2010) · Transplantation Reviews · doi:10.1016/j.trre.2010.01.002 · Cited by 39
“Low expression of the IL-7 receptor α (CD127) has been suggested to differentiate Foxp3 Tregs within the CD4CD25 population from activated T cells, which express high levels of CD127 [55,56].”
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Pozo‐Balado, M. D. M., Leal, M., Méndez‐Lagares, G., & Pacheco, Y. M. (2009) · The Journal of Infectious Diseases · doi:10.1086/649840 · Cited by 40
“A good correlation between CD4CD25CD127 and CD4CD25FoxP3 was recently reported in healthy subjects [3], and afterwards, most studies of Treg started to use this novel phenotype not only to isolate Treg, but also to directly characterize them from peripheral blood of different HIV-infected populations [4].”
BackgroundHuen, N., Pang, A. L., Tucker, J. A., Lee, T., Vergati, M., Jochéms, C., Intrivici, C., Cereda, V., Chan, W., Rennert, O. M., et al. (2013) · International Journal of Cancer · doi:10.1002/ijc.28026 · Cited by 40
“It has also been shown that CD127 expression is inversely correlated with FoxP3 expression, and that CD127(2) in the CD4(1)CD25 population confers suppressive function.(12) Tregs can suppress the immune response by a variety of mechanisms.”
BackgroundInterleukin-7 is required for CD4 + T cell activation and autoimmune neuroinflammation
Lawson, B. R., González‐Quintial, R., Eleftheriadis, T., Farrar, M. A., Miller, S. D., Sauer, K., McGavern, D. B., Kono, D. H., Baccalà, R., & Theofilopoulos, A. N. (2015) · Clinical Immunology · doi:10.1016/j.clim.2015.08.007 · Cited by 41
“Consistent with the known IL-7 requirement for T cell development and survival, this prolonged treatment resulted in reductions of thymic and peripheral T cell subsets (Table S2), but had no effects on regulatory T cells (CD4+CD25+−FoxP3+), which have been reported to express very low levels of IL-7Rα [38,39].”
ResultTremblay, J.-A., Peron, F., Kreitmann, L., Textoris, J., Brengel‐Pesce, K., Lukaszewicz, A., Quéméneur, L., Védrine, C., Tan, L., Venet, F., et al. (2022) · Annals of Intensive Care · doi:10.1186/s13613-022-01051-3 · Cited by 39
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Human treg cells are characterized by low/negative CD6 expression
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“The majority of published studies related to nTreg have used a combination of either lymphocyte-surface CD4(1)CD25 expression or, more recently, CD4(1)CD25 CD127 expression to define nTreg (19,20).”
BackgroundZaunders, J., Lévy, Y., & Seddiki, N. (2014) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2014.07.012 · Cited by 39
“Fully differentiated naı̈ve T lymphocytes reexpress IL-7R, except for a small subset of CD45RA+ Tregs [12,13].”
BackgroundSelf-citationChanges in the balance between Treg and Th17 cells in patients with chronic hepatitis B
Su, Z., Yu, X., Guo, R., Ming, D., Huang, L.-Y., Su, M., Deng, Y., & Lin, Z. (2013) · Diagnostic Microbiology and Infectious Disease · doi:10.1016/j.diagmicrobio.2013.04.026 · Cited by 39
“3 μmol/L (Imamura et al., 2003; Seddiki et al., 2006).”
T regulatory cell separation for clinical application
Ianni, M. D., Papa, B. D., Zei, T., Ostini, R. I., Cecchini, D., Cantelmi, M. G., Baldoni, S., Sportoletti, P., Cavalli, L., Carotti, A., et al. (2012) · Transfusion and Apheresis Science · doi:10.1016/j.transci.2012.06.007 · Cited by 39
“Interestingly, CD127 expression is associated with acquisition of Tregs function [16].”
BackgroundFlow Cytometric Detection of Human Regulatory T Cells
Groth, B. F. D. S., Zhu, E., Asad, S., & Lee, L. (2011) · Methods in molecular biology · doi:10.1007/978-1-61737-979-6_17 · Cited by 39
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“Changes in the frequency of Tregs (CD4+CD25+CD127low [41]) were analyzed to further characterize hHA- and MSC-mediated effects on Th cells.”
BackgroundChen, J., Zhao, L., Wang, D., Xu, Y., Gao, H., Tan, W., & Wang, C. (2018) · Molecular Medicine Reports · doi:10.3892/mmr.2018.9733 · Cited by 40
“A correlation between CD4+CD25+CD127- cells and CD4+CD25+Foxp3+ cells has been confirmed in healthy individuals (26).”
BackgroundRecent developments and highlights in immune monitoring of allergen immunotherapy
van Zelm, M. C., McKenzie, C. I., Varese, N. P., Rolland, J. M., & O’Hehir, R. E. (2019) · Allergy · doi:10.1111/all.14078 · Cited by 38
Delivery of allergen powder for safe and effective epicutaneous immunotherapy
Yu, Y., Mudnakudu-Nagaraju, K. K., & Wu, M. X. (2019) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2019.11.022 · Cited by 39
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Self-citationAdoptive regulatory T cell therapy: challenges in clinical transplantation
Safinia, N., Sagoo, P., Lechler, R. I., & Lombardi, G. (2010) · Current Opinion in Organ Transplantation · doi:10.1097/mot.0b013e32833bfadc · Cited by 40
Regulatory T cell therapy as individualized medicine for asthma and allergy
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“We then magnetically isolated CD4 + T cells and CD8 + T cells from human peripheral blood (Figure S1B) and used fl uorescence-assisted cell sorting (FACS) to further purify CD4 + CD25 hi CD127 low Tregs 36,37 and CD4 + CD25 low CD127 hi effector T (Teff) cells from the CD4 + T cells (Figure S1C).”
The regulatory T cells in anti-influenza antibody response post influenza vaccination
Wang, S.-M., Tsai, M.-H., Lei, H.-Y., Wang, J., & Liu, C. (2012) · Human Vaccines & Immunotherapeutics · doi:10.4161/hv.21117 · Cited by 39
Isolation of Purified and Live Foxp3+ Regulatory T Cells using FACS Sorting on Scatter Plot
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“Downregulation of CD127, the a chain of the IL-7 receptor, has been described as useful in the discrimination of Tregs from conventional T helper cells (Tconv) (Seddiki et al., 2006), but unfortunately, CD127 expression is also downregulated upon T cell activation and the loss of CD127 may be a characteristic feature…”
BackgroundLymphopenia and autoimmunity: A double-edged sword
Merayo‐Chalico, J., Rajme‐López, S., Barrera‐Vargas, A., Alcocer-Varela, J. C., Díaz‐Zamudio, M., & Gómez‐Martín, D. (2016) · Human Immunology · doi:10.1016/j.humimm.2016.06.016 · Cited by 41
Regulatory T Cell Metabolism in the Hepatic Microenvironment
Wawman, R. E., Bartlett, H., & Oo, Y. H. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01889 · Cited by 40
“Subsequently, Seddiki (3) and Liu (4) reported that low level expression of the IL-7 receptor, CD127, inversely correlated with FoxP3 expression and Treg cell’s suppressive function due to the repressor function of FoxP3.”
BackgroundInfluentialHope, C. M., Welch, J., Mohandas, A. P., Pederson, S., Hill, D. L., Gundsambuu, B., Eastaff‐Leung, N., Grosse, R., Bresatz, S., Ang, G., et al. (2019) · European Journal of Immunology · doi:10.1002/eji.201948094 · Cited by 38
Cabral-Marques, O., Schimke, L. F., de Oliveira, E. B., Khawanky, N. E., Ramos, R. N., al-Ramadi, B. K., Segundo, G. R. S., Ochs, H. D., & Condino‐Neto, A. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02742 · Cited by 39
Immune dysregulation increases the incidence of delayed‐type drug hypersensitivity reactions
Naisbitt, D. J., Olsson-Brown, A. C., Gibson, A., Meng, X., Ogese, M. O., Tailor, A., & Thomson, P. (2019) · Allergy · doi:10.1111/all.14127 · Cited by 40
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Biology and Clinical Observations of Regulatory T Cells in Cancer Immunology
Teng, M. W. L., Ritchie, D. S., Neeson, P. J., & Smyth, M. J. (2010) · Current topics in microbiology and immunology · doi:10.1007/82_2010_50 · Cited by 37
Development of the immune system in the human embryo
Hossain, Z., Reza, A. H. M. M., Qasem, W. A., Friel, J. K., & Omri, A. (2022) · Pediatric Research · doi:10.1038/s41390-022-01940-0 · Cited by 43
Han, Y., Wu, J., Bi, L., Xiong, S., Gao, S., Yin, L., Jiang, L., Chen, C., Kang, Y., & Zhang, S. (2011) · PLoS ONE · doi:10.1371/journal.pone.0028649 · Cited by 37
“Furthermore, they have been found that Treg express lower levels of CD127 than the majority of other CD4 T cells, and CD127 expression inversely correlates with FoxP3 expression in our own and others’ previous studies [9,10,11].”
Regulatory and effector T-cells are differentially modulated by Dexamethasone
Pandolfi, J., Baz, P., Fernández, P. M., Lupi, A. D. D., Payaslián, F., Billordo, L. A., Fainboim, L., & Arruvito, L. (2013) · Clinical Immunology · doi:10.1016/j.clim.2013.09.008 · Cited by 38
Wei, Y., Feng, J., Hou, Z., Wang, X. M., & Yu, D. (2015) · Methods in molecular biology · doi:10.1007/978-1-4939-2498-1_17 · Cited by 37
Identification, Isolation, and Functional Assay of Regulatory T Cells
Azimi, M., Aslani, S., Mortezagholi, S., Farrokhi, A. S., Javan, M. R., Rezaiemanesh, A., Ghaedi, M., Gholamzad, M., & Salehi, E. (2016) · Immunological Investigations · doi:10.1080/08820139.2016.1193869 · Cited by 36
“These results provide the potential for the isolation of nTregs without the necessity for intracellular staining (Ciebiada et al., 2013; Garcia Santana, Tung, & Gulnik 2014; Hartigan-O’Connor et al. 2007; Liu et al., 2006; Seddiki et al. 2006).”
BackgroundRestoring Regulatory T Cells in Type 1 Diabetes
Spence, A. L., & Tang, Q. (2016) · Current Diabetes Reports · doi:10.1007/s11892-016-0807-6 · Cited by 38
“The addition of the CD127 marker greatly improves the purity and yield for human Treg isolation [70, 71].”
Cohen, S., Myneni, S., Batt, A. R., Guerrero, J., Brumm, J., & Chung, S. (2021) · mAbs · doi:10.1080/19420862.2021.1898831 · Cited by 37
Bjerg, L., Brosbøl-Ravnborg, A., Tørring, C. W., Dige, A. K., Bundgaard, B. B., Petersen, T., & Höllsberg, P. (2012) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2012.04.012 · Cited by 37
“E.g. the combination of low level of IL-7 receptor α (CD127) expression with high level of CD25 expression is used to identify Foxp3+ Treg in humans (Liu et al., 2006; Seddiki et al., 2006).”
BackgroundRegulatory CD4 T cells: sensing the environment
Matarese, G., Rosa, V. D., & Cava, A. L. (2007) · Trends in Immunology · doi:10.1016/j.it.2007.10.006 · Cited by 37
Wen, X., Yang, J., James, E., Chow, I.-T., Reijonen, H., & Kwok, W. W. (2020) · Science Immunology · doi:10.1126/sciimmunol.aax8767 · Cited by 35
Immunologic unresponsiveness to alloantigen in vivo: a role for regulatory T cells
Wood, K. J., Bushell, A., & Jones, N. D. (2011) · Immunological Reviews · doi:10.1111/j.1600-065x.2011.01013.x · Cited by 37
“Recently, it has been demonstrated that CD127CD25CD4 T cells are characterized by a higher percentage of FOXP3 cells with a more pronounced suppressive capacity (146).”
BackgroundAyyoub, M., Dojcinovic, D., Pignon, P., Raimbaud, I., Schmidt, J., Luescher, I. F., & Valmori, D. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1001322107 · Cited by 36
“Another important criterion to select candidate anticancer vaccines is their ability to elicit helper CD4 T-cell responses, but not suppressive CD25CD127 Treg (16, 17).”
BackgroundCD25 Appears Non Essential for Human Peripheral Treg Maintenance In Vivo
de Herve, M.-G. D. G., Gonzales, E. M., Hendel, H., Décline, J.-L., Mourier, O., Abbed, K., Jacquemin, E., & Taoufik, Y. (2010) · PLoS ONE · doi:10.1371/journal.pone.0011784 · Cited by 37
“No significant change in IL-15Ra or IL-7Ra expression on FoxP3+ CD4 T cells following basiliximab administration As mentioned above, another possibility is that Tregs use a substitute cytokine such as IL-15 when CD25 is unavailable.”
BackgroundInfluentialBuccione, C., Fragale, A., Polverino, F., Ziccheddu, G., Aricò, E., Belardelli, F., Proietti, E., Battistini, A., & Moschella, F. (2017) · International Journal of Cancer · doi:10.1002/ijc.31083 · Cited by 36
Atif, M., Warner, S., & Oo, Y. H. (2018) · Hepatology International · doi:10.1007/s12072-018-9882-x · Cited by 35
Human CD4+CD25highCD127low/neg Regulatory T Cells
Su, H., Longhi, M. S., Wang, P., Mieli‐Vergani, G., & Ma, Y. (2011) · Methods in molecular biology · doi:10.1007/978-1-61779-367-7_20 · Cited by 36
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Gendron, S., Boisvert, M., Chetoui, N., & Aoudjit, F. (2008) · Immunology · doi:10.1111/j.1365-2567.2008.02858.x · Cited by 36
Li, Y., Fu, R., Liu, H., Wang, H., Liu, C., Wang, T., Qi, W., Guan, J. Z., Li, L., & Shao, Z. (2015) · Cellular Immunology · doi:10.1016/j.cellimm.2015.04.001 · Cited by 36
Maturation of CD4+ Regulatory T Lymphocytes and of Cytokine Secretions in Infants Born Prematurely
Dirix, V., Vermeulen, F. L., & Mascart, F. (2013) · Journal of Clinical Immunology · doi:10.1007/s10875-013-9911-4 · Cited by 36
“It is recommended to combine this marker with a low expression of CD127 and/or an intracellular expression of FoxP3, to allow a more precise identification of Treg lymphocytes [27, 28], even if the percentages of CD25Foxp3 and of CD25 CD127 among CD4 T cells are poorly correlated.”
BackgroundResultT regulatory cells lacking CD25 are increased in MS during relapse
Fransson, M. E., Burman, J., Lindqvist, C. A., Atterby, C., Fagius, J., & Loskog, A. (2010) · Autoimmunity · doi:10.3109/08916930903541190 · Cited by 36
“populations using multicolor flow cytometry [11].”
Shen, T., Zheng, J., Liang, H. L., Xu, C., Chen, X., Zhang, T., Xu, Q., & Lu, F. (2011) · Virology Journal · doi:10.1186/1743-422x-8-279 · Cited by 36
“Discussion Both CD4CD127CD25 and CD4FoxP3were classic phenotypes of regulatory CD4 T cells, which has been described by accumulating literatures [34-36].”
BackgroundUnravelling the molecular basis for regulatory T‐cell plasticity and loss of function in disease
Sadlon, T. J., Brown, C. Y., Bandara, V., Hope, C. M., Schjenken, J. E., Pederson, S., Breen, J., Forrest, A. R. R., Beyer, M., Robertson, S. A., et al. (2018) · Clinical & Translational Immunology · doi:10.1002/cti2.1011 · Cited by 38
“More recently, a search for cell surface surrogates of FOXP3 (FOXP3 cannot be used to isolate viable Treg as it requires intracellular staining) has revealed that reduced expression of the IL7 receptor (CD127) is also a hallmark of the human Treg phenotype.(7,8) It has been reported that CD127 is not selective for mou…”
BackgroundWang, Y. N., Zhang, Y., Wang, Y., Zhu, D. X., Xu, L., Fang, H., & Wu, W. (2013) · Phytotherapy Research · doi:10.1002/ptr.5005 · Cited by 35
“Recently, however, IL-7Ra (CD127) expression has emerged as a more useful marker for discriminating CD4+CD25+ Tregs from activated T cells (Seddiki et al., 2006).”
BackgroundHaridas, V., Pean, P., Jasenosky, L. D., Madec, Y., Laureillard, D., Thim, S., Sath, S., Borand, L., Marcy, O., Chan, S., et al. (2014) · AIDS · doi:10.1097/qad.0000000000000546 · Cited by 34
“To determine whether regulatory CD4þ T-cell (CD4þ Treg) frequencies differed between TB-IRIS and nonTB-IRIS patients, we employed surface staining to enumerate CD25þCD127loCD4þ T cells [10–12].”
MethodRapid assessment of in vitro expanded human regulatory T cell function
Ruitenberg, J. J., Boyce, C. S., Hingorani, R., Putnam, A. L., & Ghanekar, S. (2011) · Journal of Immunological Methods · doi:10.1016/j.jim.2011.07.001 · Cited by 35
Żabińska, M., Krajewska, M., Kościelska−Kasprzak, K., Jakuszko, K. J., Bartoszek, D., Myszka, M., & Klinger, M. (2016) · Archivum Immunologiae et Therapiae Experimentalis · doi:10.1007/s00005-016-0399-5 · Cited by 35
“The correlation between CD4CD25CD127 and CD4 CD25Foxp3 cells has been confirmed in healthy individuals (Seddiki et al. 2006), but as in the case of CD25 molecule, CD127 expression is significantly reduced after stimulation, which makes it difficult to be used as an identifier of regulatory cells (Aerts et al.”
Fleury, M., Belkina, A. C., Proctor, E. A., Zammitti, C. A., Simms, R. W., Lauffenburger, D. A., Snyder-Cappione, J. E., Lafyatis, R., & Dooms, H. (2017) · Arthritis & Rheumatology · doi:10.1002/art.40399 · Cited by 34
“Within the CD4+ T cells, high expression levels of CD25 and low levels of CD127 were used to delineate a population enriched in regulatory T cells, hereinafter referred to as Treg cells (17,18).”
Fu, J., Duan, J., Mo, J., Xiao, H., Huang, Y., Chen, W., Xiang, S., Yang, F., Chen, Y., & Xu, S. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.624304 · Cited by 36
“Immunoregulatory cells— regulatory T-cells (Tregs) [cell phenotype can be defined as CD4CD25Foxp3, Tregs hardly express CD127, so they can also be expressed by CD4+CD25+CD127low/− (Seddiki et al., 2006)], participate in this important regulatory mechanism through the secretion of anti-inflammatory cytokines, such as i…”
BackgroundInfluentialKasow, K. A., Morales-Tirado, V. M., Wichlan, D., Shurtleff, S. A., Abraham, A., Persons, D. A., & Riberdy, J. M. (2011) · Clinical Immunology · doi:10.1016/j.clim.2011.07.005 · Cited by 35
Esquerré, M., Tauzin, B., Guiraud, M., Müller, S., Saoudi, A., & Valitutti, S. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0708350105 · Cited by 35
Do regulatory T-cells play a role in AIDS pathogenesis?
Boasso, A., Vaccari, M., Nilsson, J., Gm, S., Andersson, J., Cecchinato, V., Chougnet, C. A., & Franchini, G. (2006) · PubMed · Cited by 34
OMIP‐015: Human regulatory and activated T‐cells without intracellular staining
Mahnke, Y. D., Beddall, M. H., & Roederer, M. (2013) · Cytometry Part A · doi:10.1002/cyto.a.22230 · Cited by 34
“A combined measurement of the IL-2Ra chain (CD25) and the IL-7R a-chain (CD127) was used, with Treg being defined as CD25 CD127(2) (3).”
BackgroundMethodD'Arena, G. F., D’Auria, F., Simeon, V., Laurenti, L., Deaglio, S., Mansueto, G., Principe, M. I. D., Statuto, T., Pietrantuono, G., Guariglia, R., et al. (2012) · American Journal of Hematology · doi:10.1002/ajh.23170 · Cited by 34
“This gating strategy was chosen because it better discriminates between Treg cells and activated T-cells that normally upregulate CD25 antigen [14].”
BackgroundBeyer, M., Claßen, S., Endl, E., Kochanek, M., Weihrauch, M. R., Debey‐Pascher, S., Knolle, P. A., & Schultze, J. L. (2011) · Clinical and Developmental Immunology · doi:10.1155/2011/734036 · Cited by 34
“7%) were similar to previously published results (Figure 3(c) and Table 3) [2, 5, 6, 24].”
BackgroundResultCirculating T cell subsets are altered in individuals with chronic spinal cord injury
Monahan, R., Stein, A., Gibbs, K., Bank, M. A., & Bloom, O. (2015) · Immunologic Research · doi:10.1007/s12026-015-8698-1 · Cited by 34
“CD127, the alpha chain of the IL-7 receptor, is inversely correlated with FoxP3? in human TRegs [31, 32] and in combination with CD25? high CD4?”
BackgroundInfluentialBetts, B. C., Veerapathran, A., Pidala, J., Yu, X., & Anasetti, C. (2013) · Journal of Leukocyte Biology · doi:10.1189/jlb.0313154 · Cited by 34
“Small-molecule inhibitors included S3I-201 (STAT3) and CAS 285986-31-4 (STAT5) (EMD Millipore, Billerica, MA, USA), diluted in DMSO ( 0.1% v/v). mAbs and flow cytometry Fluorochrome-conjugated mouse anti-human mAbs included anti-CD3, -CD4, -CD8, -CD25, -CD45RO, -CD107a, -CD127, -Foxp3, -pSTAT3/pY705, -pSTAT5/ pY694, -…”
BackgroundMethodInfluentialTan, D. B. A., Fernández, S., Price, P., French, M. A., Thompson, P. J., & Moodley, Y. P. (2014) · Immunobiology · doi:10.1016/j.imbio.2014.07.005 · Cited by 34
Turner, B. E., Kambouris, M. E., Sinfield, L. J., Lange, J., Burns, A.-M., Lourie, R., Atkinson, K., Hart, D. N. J., Munster, D. J., & Rice, A. M. (2008) · Transplantation · doi:10.1097/tp.0b013e3181874787 · Cited by 34
“T-regulatory cells were analyzed using the following phenotype: (CD3 CD4 CD25CD127) (26) or using a FoxP3 kit (CD4 CD25 Foxp3 ) (27) (eBiosciences, San Diego, CA).”
BackgroundMethodŁuczyński, W., Wawrusiewicz‐Kurylonek, N., Stasiak‐Barmuta, A., Urban, R., Iłendo, E., Urban, M., Hryszko, M., Kretowski, A. J., & Górska, M. (2009) · Acta Biochimica Polonica · doi:10.18388/abp.2009_2469 · Cited by 34
“Low or negative cell surface expression of CD127 antigen provides a flexible alternative to the FoxP3 for identifying and isolating T regulatory cells for functional analysis (Seddiki et al., 2006).”
BackgroundWild, C. A. (2010) · Archives of Otolaryngology - Head and Neck Surgery · doi:10.1001/archoto.2010.195 · Cited by 34
HIV infection perturbs interleukin-7 signaling at the step of STAT5 nuclear relocalization
Landires, I., Bugault, F., Lambotte, O., de Truchis, P., Slama, L., Danckaert, A., Delfraissy, J., Thèze, J., & Chakrabarti, L. A. (2011) · AIDS · doi:10.1097/qad.0b013e32834a3678 · Cited by 34
“Because regulatory T cells (Tregs) respond less efficiently to IL-7 than conventional memory CD4þT cells [31,32], a separate analysis was carried out to evaluate STAT5 phosphorylation in the Treg population.”
BackgroundResearch advances on targeted-Treg therapies on immune-mediated kidney diseases
Li, Y., Liu, H., Yan, H., & Xiong, J. (2022) · Autoimmunity Reviews · doi:10.1016/j.autrev.2022.103257 · Cited by 33
Regulatory T cell response correlates with the severity of human hantavirus infection
Koivula, T.-T., Tuulasvaara, A., Hetemäki, I., Mäkelä, S., Mustonen, J. T., Sironen, T. A., Vaheri, A. I., & Arstila, T. P. (2013) · Journal of Infection · doi:10.1016/j.jinf.2013.11.007 · Cited by 34
Steinborn, A., Engst, M., Haensch, G. M., Mahnke, K., Schmitt, E., Meuer, S. C., & Sohn, C. (2009) · Clinical Immunology · doi:10.1016/j.clim.2009.09.003 · Cited by 33
Vercoulen, Y., Wehrens, E. J., van Teijlingen, N. H., de Jager, W., Beekman, J. M., & Prakken, B. J. (2009) · PLoS ONE · doi:10.1371/journal.pone.0007183 · Cited by 37
“PLoS ONE | www.plosone.org 5 September 2009 | Volume 4 | Issue 9 | e7183 PLoS ONE | www.plosone.org 6 September 2009 | Volume 4 | Issue 9 | e7183 Suppression assay CD4+ CD252 effector T cells (Teff), were magnetically isolated from PBMC using a CD4 T Lymphocyte Enrichment Set (BD Biosciences).”
BackgroundInfluentialTranslating tolerogenic therapies to the clinic – where do we stand?
Issa, F., & Wood, K. J. (2012) · Frontiers in Immunology · doi:10.3389/fimmu.2012.00254 · Cited by 33
Zhang, H., Guo, H., Lu, L., Zahorchak, A. F., Wiseman, R. W., Raimondi, G., Cooper, D. K. C., Ezzelarab, M. B., & Thomson, A. W. (2015) · American Journal of Transplantation · doi:10.1111/ajt.13113 · Cited by 33
“The regulatory function of human nTreg (15–18) is associated with sustained levels of Foxp3 and low CD127 (IL-7R) expression (19,20).”
Mesa, M. C., Gutiérrez, L. C., Duarte-Rey, C., Ángel, J., & Franco, M. A. (2010) · Virology · doi:10.1016/j.virol.2009.12.016 · Cited by 33
“cells) (Seddiki et al., 2006) we found in children with GE are similar to those reported for the same age group in healthy children, suggesting that GE, and RV GE in particular, do not change the frequencies of these peripheral Treg cells (Fuchizawa et al.”
BackgroundResultInfluentialHall, B. M., Tran, G. T., Verma, N. D., Plain, K. M., Robinson, C. M., Nomura, M., & Hodgkinson, S. J. (2013) · Frontiers in Immunology · doi:10.3389/fimmu.2013.00208 · Cited by 34
“Natural Treg have low expression of CD127, the IL-7 receptor, which is highly expressed by effector lineage CD4CD25 T cells (26), albeit activated CD4 T cells (27), and T follicular helper cells (Tfh) also have low expression of CD127 (28).”
BackgroundLim, A. Y. F., French, M. A., & Price, P. (2009) · JAIDS Journal of Acquired Immune Deficiency Syndromes · doi:10.1097/qai.0b013e3181a74fad · Cited by 33
“These included cytotoxic T lymphocyte–associated antigen (CTLA)-4, glucocorticoid-induced tumor necrosis factor receptor–related gene (GITR),21–24 and programmed death (PD)-1, which is an inhibitory receptor of the CD28/CTLA-4 family and is induced upon T-cell activation25,26 and low expression of CD127.”
BackgroundHinz, D., Simon, J. C., Maier‐Simon, C., Milkova, L., Röder, S. W., Sack, U., Borte, M., Lehmann, I., & Herberth, G. (2010) · Clinical & Experimental Allergy · doi:10.1111/j.1365-2222.2009.03434.x · Cited by 33
Regulatory T Cells in Allogeneic Stem Cell Transplantation
Michael, M., Shimoni, A., & Nagler, A. (2013) · Clinical and Developmental Immunology · doi:10.1155/2013/608951 · Cited by 33
Increased frequencies of pulmonary regulatory T-cells in latentMycobacterium tuberculosisinfection
Herzmann, C., Ernst, M., Ehlers, S., Stenger, S., Maertzdorf, J., Sotgiu, G., & Lange, C. G. (2012) · European Respiratory Journal · doi:10.1183/09031936.00214611 · Cited by 34
Choi, Y. S., Jung, M. K., Lee, J., Choi, S. J., Choi, S. H., Lee, H. W., Lee, J.-J., Kim, H. J., Ahn, S. H., Lee, D. H., et al. (2017) · Gastroenterology · doi:10.1053/j.gastro.2017.11.277 · Cited by 35
Beyond FOXP3: a 20-year journey unravelling human regulatory T-cell heterogeneity
Nirmala, S. S., Kayani, K., Gliwiński, M., Hu, Y., Iwaszkiewicz‐Grześ, D., Piotrowska, M., Sakowska, J., Tomaszewicz, M., Morales, J. M. M., Lakshmi, K., et al. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1321228 · Cited by 37
Regulating the regulators in cancer-immunosuppression in multiple myeloma (MM)
Feyler, S., Selby, P. J., & Cook, G. (2013) · Blood Reviews · doi:10.1016/j.blre.2013.04.004 · Cited by 32
Szalay, B., Mészáros, G., Cseh, Á., Ács, L., Deák, M., Kovács, L., Vásárhelyi, B., & Balog, A. (2011) · Clinical and Developmental Immunology · doi:10.1155/2012/808724 · Cited by 32
“While Wu et al. identified Tregs according to FoxP3 expression, we defined Tregs as CD4+CD25+CD127−.”
ResultItose, I., Kanto, T., Kakita, N., Takebe, S., Inoue, M., Higashitani, K., Miyazaki, M., Miyatake, H., Sakakibara, M., Hiramatsu, N., et al. (2009) · Journal of Viral Hepatitis · doi:10.1111/j.1365-2893.2009.01131.x · Cited by 32
Xufré, C., Costa, M., Roura‐Mir, C., Busqueta, E. C., Usero, L., Pizarro, E., Obiols, G., Jaraquemada, D., & Martı́, M. (2013) · International Immunology · doi:10.1093/intimm/dxt020 · Cited by 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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