Cited by 402T-cell and B-cell ImmunologyHematopoietic Stem Cell TransplantationRenal Transplantation Outcomes and Treatments

The DOI matches its Crossref record; 51 of the 52 references it cites were found in a registry or an index.

Differential impact of mammalian target of rapamycin inhibition on CD4 +CD25+Foxp3+ regulatory T cells compared with conventional CD4+ T cells

Open access

Zeiser, Robert, Leveson-Gower, Dennis B., Zambricki, Elizabeth A., Kambham, Neeraja, Beilhack, Andreas, Loh, John, Hou, Jing-Zhou, Negrin, Robert S.·2008·Blood

DOI 10.1182/blood-2007-06-094482PMC PMC2200823

Open this paper in CoChat — free account Open PDF

Abstract

Based on their ability to control T-cell homeostasis, Foxp3+CD4+CD25+ regulatory T cells (Tregs) are being considered for treatment of autoimmune disorders and acute graft-versus-host disease (aGVHD). When combining Tregs with the immunosuppressant rapamycin (RAPA), we observed reduced alloreactive conventional T-cell (Tconv) expansion and aGVHD lethality compared with each treatment alone. This synergistic in vivo protection was paralleled by intact expansion of polyclonal Tregs with conserved high FoxP3 expression. In contrast to Tconv, activation of Tregs with alloantigen and interleukin-2 preferentially led to signal transducer and activator of transcription 5 (STAT5) phosphorylation and not phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway activity. Expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a negative regulator of the PI3K/Akt/mTOR pathway, remained high in Tregs but not Tconv during stimulation. Conversely, targeted deletion of PTEN increased susceptibility of Tregs to mTOR inhibition by RAPA. Differential impact of RAPA as a result of reduced usage of the mTOR pathway in Tregs compared with conventional T cells explains the synergistic effect of RAPA and Tregs in aGVHD protection, which has important implications for clinical trials using Tregs.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1182/blood-2007-06-094482

Cites

51 of 51 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

N aturally A rising CD4+R egulatory T C ells for I mmunologic S elf -T olerance and N egative C ontrol of I mmune R esponses
Sakaguchi, S. (2003) · Annual Review of Immunology · doi:10.1146/annurev.immunol.21.120601.141122 · Cited by 3,315
Causal Protein-Signaling Networks Derived from Multiparameter Single-Cell Data
Sachs, K., Perez, O. D., Pe’er, D., Lauffenburger, D. A., & Nolan, G. P. (2005) · Science · doi:10.1126/science.1105809 · Cited by 1,785
Stimulation of CD25(+)CD4(+) regulatory T cells through GITR breaks immunological self-tolerance
Shimizu, J., Yamazaki, S., Takahashi, T., Ishida, Y., & Sakaguchi, S. (2002) · Nature Immunology · doi:10.1038/ni759 · Cited by 1,729
CD4+CD25+ Immunoregulatory T Cells
McHugh, R. S., Whitters, M. J., Piccirillo, C. A., Young, D. A., Shevach, E. M., Collins, M., & Byrne, M. C. (2002) · Immunity · doi:10.1016/s1074-7613(02)00280-7 · Cited by 1,395
CD4+CD25+ regulatory T cells preserve graft-versus-tumor activity while inhibiting graft-versus-host disease after bone marrow transplantation
Edinger, M., Hoffmann, P., Ermann, J., Drago, K., Fathman, C. G., Strober, S., & Negrin, R. S. (2003) · Nature Medicine · doi:10.1038/nm915 · Cited by 1,286
Self-citation
FOXP3 Controls Regulatory T Cell Function through Cooperation with NFAT
Wu, Y., Borde, M., Heissmeyer, V., Feuerer, M., Lapan, A. D., Stroud, J. C., Bates, D. L., Guo, L., Han, A., Ziegler, S. F., et al. (2006) · Cell · doi:10.1016/j.cell.2006.05.042 · Cited by 1,229
Rapamycin selectively expands CD4+CD25+FoxP3+ regulatory T cells.
Battaglia, M., Stabilini, A., & Roncarolo, M. (2005) · Blood · doi:10.1182/blood-2004-10-3932 · Cited by 1,203
IL-2 Receptor β-Dependent STAT5 Activation Is Required for the Development of Foxp3+ Regulatory T Cells
Burchill, M. A., Yang, J., Vogtenhuber, C., Blazar, B. R., & Farrar, M. A. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.1.280 · Cited by 831
Rapamycin Promotes Expansion of Functional CD4+CD25+FOXP3+ Regulatory T Cells of Both Healthy Subjects and Type 1 Diabetic Patients
Battaglia, M., Stabilini, A., Migliavacca, B., Horejs‐Hoeck, J., Kaupper, T., & Roncarolo, M. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.12.8338 · Cited by 746
CD25+CD4+ Regulatory T Cells Prevent Graft Rejection: CTLA-4- and IL-10-Dependent Immunoregulation of Alloresponses
Kingsley, C. I., Karim, M., Bushell, A., & Wood, K. J. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.168.3.1080 · Cited by 742

Show all 52 references

Sorted by citations

Short-chain fatty acids induce both effector and regulatory T cells by suppression of histone deacetylases and regulation of the mTOR–S6K pathway
Park, J., Kim, M., Kang, S. G., Jannasch, A. H., Cooper, B., Patterson, J., & Kim, C. H. (2015) · Mucosal Immunology · doi:10.1038/mi.2014.44 · Cited by 1,307
Acute Graft-versus-Host Disease — Biologic Process, Prevention, and Therapy
Zeiser, R., & Blazar, B. R. (2017) · New England Journal of Medicine · doi:10.1056/nejmra1609337 · Cited by 1,347
Self-citation
Infusion of ex vivo expanded T regulatory cells in adults transplanted with umbilical cord blood: safety profile and detection kinetics
Brunstein, C. G., Miller, J. S., Cao, Q., McKenna, D. H., Hippen, K. L., Curtsinger, J., DeFor, T. E., Levine, B. L., June, C. H., Rubinstein, P., et al. (2010) · Blood · doi:10.1182/blood-2010-07-293795 · Cited by 1,052
Regulation and function of mTOR signalling in T cell fate decisions
Chi, H. (2012) · Nature Reviews Immunology · doi:10.1038/nri3198 · Cited by 1,035
Signaling and Function of Interleukin-2 in T Lymphocytes
Ross, S. H., & Cantrell, D. A. (2018) · Annual Review of Immunology · doi:10.1146/annurev-immunol-042617-053352 · Cited by 1,025
Immunoregulatory functions of mTOR inhibition
Thomson, A. W., Turnquist, H. R., & Raimondi, G. (2009) · Nature reviews. Immunology · doi:10.1038/nri2546 · Cited by 873
Regulation of Immune Responses by mTOR
Powell, J. D., Pollizzi, K. N., Heikamp, E. B., & Horton, M. R. (2012) · Annual Review of Immunology · doi:10.1146/annurev-immunol-020711-075024 · Cited by 836
T cell receptor signalling in the control of regulatory T cell differentiation and function
Li, M. O., & Rudensky, A. Y. (2016) · Nature Reviews Immunology · doi:10.1038/nri.2016.26 · Cited by 493
The Mammalian Target of Rapamycin: Linking T Cell Differentiation, Function, and Metabolism
Powell, J. D., & Delgoffe, G. M. (2010) · Immunity · doi:10.1016/j.immuni.2010.09.002 · Cited by 503
The Biology of Chronic Graft-versus-Host Disease: A Task Force Report from the National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease
Cooke, K. R., Luznik, L., Sarantopoulos, S., Hakim, F. T., Jagasia, M., Fowler, D. H., van den Brink, M. R. M., Hansen, J. A., Parkman, R., Miklos, D. B., et al. (2016) · Transplantation and Cellular Therapy · doi:10.1016/j.bbmt.2016.09.023 · Cited by 483
Graft-versus-host disease is enhanced by extracellular ATP activating P2X7R
Wilhelm, K., Ganesan, J., Müller, T., Dürr, C., Grimm, M., Beilhack, A., Krempl, C. D., Sorichter, S., Gerlach, U. V., Jüttner, E., et al. (2010) · Nature Medicine · doi:10.1038/nm.2242 · Cited by 435
Self-citation
mTOR , metabolism, and the regulation of T‐cell differentiation and function
Waickman, A. T., & Powell, J. D. (2012) · Immunological Reviews · doi:10.1111/j.1600-065x.2012.01152.x · Cited by 420
Control of PI(3) kinase in Treg cells maintains homeostasis and lineage stability
Huynh, A., DuPage, M. J. P., Priyadharshini, B., Sage, P. T., Quiros, J., Borges, C. M., Townamchai, N., Gerriets, V. A., Rathmell, J. C., Sharpe, A. H., et al. (2015) · Nature Immunology · doi:10.1038/ni.3077 · Cited by 412
Activity of therapeutic JAK 1/2 blockade in graft-versus-host disease
Spoerl, S., Mathew, N. R., Bscheider, M., Schmitt-Graeff, A. H., Chen, S., Mueller, T., Verbeek, M., Fischer, J. C., Otten, V., Schmickl, M., et al. (2014) · Blood · doi:10.1182/blood-2013-12-543736 · Cited by 421
Self-citation
NK cells mediate reduction of GVHD by inhibiting activated, alloreactive T cells while retaining GVT effects
Olson, J. A., Leveson-Gower, D. B., Gill, S. I., Baker, J. B., Beilhack, A., & Negrin, R. S. (2010) · Blood · doi:10.1182/blood-2009-05-222190 · Cited by 387
Self-citation
Human regulatory T cells: role in autoimmune disease and therapeutic opportunities
Brusko, T. M., Putnam, A. L., & Bluestone, J. A. (2008) · Immunological Reviews · doi:10.1111/j.1600-065x.2008.00637.x · Cited by 379
Expansion of Human Regulatory T-Cells From Patients With Type 1 Diabetes
Putnam, A. L., Brusko, T. M., Lee, M. R., Liu, W., Szot, G. L., Ghosh, T., Atkinson, M. A., & Bluestone, J. A. (2008) · Diabetes · doi:10.2337/db08-1168 · Cited by 363
Neutrophil granulocytes recruited upon translocation of intestinal bacteria enhance graft-versus-host disease via tissue damage
Schwab, L., Goroncy, L., Palaniyandi, S., Gautam, S., Triantafyllopoulou, A., Mócsai, A., Reichardt, W., Karlsson, F. J., Radhakrishnan, S. V., Hanke, K., et al. (2014) · Nature Medicine · doi:10.1038/nm.3517 · Cited by 302
Self-citation
Acute graft-versus-host disease: from the bench to the bedside
Socié, G., & Blazar, B. R. (2009) · Blood · doi:10.1182/blood-2009-06-204669 · Cited by 268
TLR8-Mediated Metabolic Control of Human Treg Function: A Mechanistic Target for Cancer Immunotherapy
Li, L., Liu, X., Sanders, K. L., Edwards, J. L., Ye, J., Si, F., Gao, A., Huang, L., Hsueh, E. C., Ford, D. A., et al. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.09.020 · Cited by 248
Treg Enhancing Therapies to Treat Autoimmune Diseases
Eggenhuizen, P. J., Ng, B. H., & Ooi, J. D. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21197015 · Cited by 252
The Nlrp3 inflammasome regulates acute graft-versus-host disease
Jankovic, D. L., Ganesan, J., Bscheider, M., Stickel, N., Weber, F. C., Guarda, G., Follo, M., Pfeifer, D., Tardivel, A., Ludigs, K., et al. (2013) · The Journal of Experimental Medicine · doi:10.1084/jem.20130084 · Cited by 241
Self-citation
Regulatory T-Cell Therapy in Transplantation: Moving to the ClinicPreprint
Tang, Q., & Bluestone, J. A. (2013) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a015552 · Cited by 237
Metabolic control of the Treg/Th17 axis
Barbi, J. J., Pardoll, D. M., & Pan, F. (2013) · Immunological Reviews · doi:10.1111/imr.12029 · Cited by 227
Regulation of T cells by mTOR: the known knowns and the known unknowns
Pollizzi, K. N., & Powell, J. D. (2014) · Trends in Immunology · doi:10.1016/j.it.2014.11.005 · Cited by 202
Production of IL-10 by CD4+ regulatory T cells during the resolution of infection promotes the maturation of memory CD8+ T cells
Laidlaw, B. J., Cui, W., Amezquita, R. A., Gray, S. M., Guan, T., Lu, Y., Kobayashi, Y., Flavell, R. A., Kleinstein, S. H., Craft, J. E., et al. (2015) · Nature Immunology · doi:10.1038/ni.3224 · Cited by 199
Cutting Edge: Foxp3-Mediated Induction of Pim 2 Allows Human T Regulatory Cells to Preferentially Expand in Rapamycin
Basu, S., Golovina, T. N., Mikheeva, T., June, C. H., & Riley, J. L. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.9.5794 · Cited by 183
Regulatory T Cells as Immunotherapy
Singer, B. D., King, L. S., & D’Alessio, F. R. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00046 · Cited by 187
Local immunomodulation with Fas ligand-engineered biomaterials achieves allogeneic islet graft acceptance
Headen, D. M., Woodward, K. B., Coronel, M. M., Shrestha, P., Weaver, J. D., Zhao, H., Tan, M., Hunckler, M. D., Bowen, W. S., Johnson, C. T., et al. (2018) · Nature Materials · doi:10.1038/s41563-018-0099-0 · Cited by 175
Immunosuppression for in vivo research: state-of-the-art protocols and experimental approaches
Diehl, R., Ferrara, F., Müller, C., Dreyer, A. Y., McLeod, D. D., Fricke, S., & Boltze, J. (2016) · Cellular and Molecular Immunology · doi:10.1038/cmi.2016.39 · Cited by 172
Differential Responses of Human Regulatory T Cells (Treg) and Effector T Cells to Rapamycin
Strauss, L., Czystowska, M., Szajnik, M. E., Mandapathil, M., & Whiteside, T. L. (2009) · PLoS ONE · doi:10.1371/journal.pone.0005994 · Cited by 170
Regulatory T cells in stem cell transplantation: strategies and first clinical experiences
Edinger, M., & Hoffmann, P. (2011) · Current Opinion in Immunology · doi:10.1016/j.coi.2011.06.006 · Cited by 172
CD4+Foxp3+ regulatory T cell therapy in transplantation
Tang, Q., Bluestone, J. A., & Kang, S. (2011) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjr047 · Cited by 161
CHAI and LATAIE: new genetic diseases of CTLA-4 checkpoint insufficiency
Lo, B., Fritz, J. M., Su, H. C., Uzel, G., Jordan, M. B., & Lenardo, M. J. (2016) · Blood · doi:10.1182/blood-2016-04-712612 · Cited by 155
Rapamycin and IL-2 reduce lethal acute graft-versus-host disease associated with increased expansion of donor type CD4+CD25+Foxp3+ regulatory T cells.
Shin, H., Baker, J., Leveson-Gower, D., Smith, A. T., Sega, E. I., & Negrin, R. (2011) · Blood · doi:10.1182/blood-2010-10-313684 · Cited by 160
Self-citation
mTOR Signaling, Tregs and Immune Modulation
Chapman, N. M., & Chi, H. (2014) · Immunotherapy · doi:10.2217/imt.14.84 · Cited by 148
mTOR Complex 1 Signaling Regulates the Generation and Function of Central and Effector Foxp3+ Regulatory T Cells
Sun, I., Oh, M. H., Zhao, L., Patel, C. H., Arwood, M. L., Xu, W., Tam, A. J., Blosser, R. L., Wen, J., & Powell, J. D. (2018) · The Journal of Immunology · doi:10.4049/jimmunol.1701477 · Cited by 142
Frequency of CD4+CD25hiFOXP3+ Regulatory T Cells Has Diagnostic and Prognostic Value as a Biomarker for Acute Graft-versus-Host-Disease
Magenau, J. M., Qin, X., Tawara, I., Rogers, C. E., Kitko, C. L., Schlough, M., Bickley, D., Braun, T., Jang, P., Lowler, K. P., et al. (2010) · Transplantation and Cellular Therapy · doi:10.1016/j.bbmt.2010.02.026 · Cited by 143
A Rapamycin-Based GMP-Compatible Process for the Isolation and Expansion of Regulatory T Cells for Clinical Trials
Fraser, H., Safinia, N., Grageda, N., Thirkell, S., Lowe, K., Fry, L., Scottà, C., Hope, A. J., Fisher, C., Hilton, R. M., et al. (2018) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2018.01.006 · Cited by 141
Immunosuppression for liver transplantation
Geissler, E. K., & Schlitt, H. J. (2008) · Gut · doi:10.1136/gut.2008.163527 · Cited by 139
Treg-Therapy Allows Mixed Chimerism and Transplantation Tolerance Without Cytoreductive Conditioning
Pilat, N., Baranyi, U., Klaus, C., Jaeckel, E., Mpofu, N., Wrba, F., Golshayan, D., Muehlbacher, F., & Wekerle, T. (2010) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2010.03018.x · Cited by 141
Identification and expansion of highly suppressive CD8+FoxP3+ regulatory T cells after experimental allogeneic bone marrow transplantation
Robb, R. J., Lineburg, K. E., Kuns, R. D., Wilson, Y. A., Raffelt, N. C., Olver, S. D., Varelias, A., Alexander, K. A., Teal, B. E., Sparwasser, T. D., et al. (2012) · Blood · doi:10.1182/blood-2011-12-396119 · Cited by 136
Alpha-1-antitrypsin monotherapy reduces graft-versus-host disease after experimental allogeneic bone marrow transplantation
Tawara, I., Sun, Y., Lewis, E. C., Toubai, T., Evers, R., Nieves, E. C., Azam, T., Dinarello, C. A., & Reddy, P. R. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1117665109 · Cited by 134
Allogeneic CAR Cell Therapy—More Than a Pipe Dream
Caldwell, K. J., Gottschalk, S. M., & Talleur, A. C. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2020.618427 · Cited by 141
The STAT5b Pathway Defect and Autoimmunity
Kanai, T., Jenks, J. A., & Nadeau, K. C. (2012) · Frontiers in Immunology · doi:10.3389/fimmu.2012.00234 · Cited by 132
STAT5b Deficiency: An Unsuspected Cause of Growth Failure, Immunodeficiency, and Severe Pulmonary Disease
Nadeau, K. C., Hwa, V., & Rosenfeld, R. G. (2011) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2010.12.042 · Cited by 128
Impact of Immune-Modulatory Drugs on Regulatory T Cell
Furukawa, A., Wisel, S. A., & Tang, Q. (2016) · Transplantation · doi:10.1097/tp.0000000000001379 · Cited by 130
De novo induction of antigen-specific CD4+CD25+Foxp3+ regulatory T cells in vivo following systemic antigen administration accompanied by blockade of mTOR
Kang, J., Huddleston, S. J., Fraser, J. M., & Khoruts, A. (2008) · Journal of Leukocyte Biology · doi:10.1189/jlb.1207851 · Cited by 126
Gene editing to induce FOXP3 expression in human CD4 + T cells leads to a stable regulatory phenotype and function
Honaker, Y., Hubbard, N., Xiang, Y., Fisher, L., Hagin, D., Sommer, K., Song, Y., Yang, S. J., Lopez, C., Tappen, T., et al. (2020) · Science Translational Medicine · doi:10.1126/scitranslmed.aay6422 · Cited by 126
mTOR, Cancer and Transplantation
Geissler, E. K., Schlitt, H. J., & Thomas, G. (2008) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2008.02391.x · Cited by 122
Role of T cells in graft rejection and transplantation tolerance
Issa, F., Șchiopu, A., & Wood, K. J. (2009) · Expert Review of Clinical Immunology · doi:10.1586/eci.09.64 · Cited by 126
Induced Regulatory T Cells Promote Tolerance When Stabilized by Rapamycin and IL-2 In Vivo
Zhang, P., Tey, S., Koyama, M., Kuns, R. D., Olver, S. D., Lineburg, K. E., Lor, M., Teal, B. E., Raffelt, N. C., Raju, J., et al. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1301181 · Cited by 120
Regulatory T Cells: Serious Contenders in the Promise for Immunological Tolerance in Transplantation
Safinia, N., Scottà, C., Vaikunthanathan, T., Lechler, R. I., & Lombardi, G. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00438 · Cited by 119
Progesterone suppresses the m TOR pathway and promotes generation of induced regulatory T cells with increased stability
Lee, J. H., Lydon, J. P., & Kim, C. H. (2012) · European Journal of Immunology · doi:10.1002/eji.201142317 · Cited by 118
Low doses of natural killer T cells provide protection from acute graft-versus-host disease via an IL-4–dependent mechanism
Leveson-Gower, D. B., Olson, J. A., Sega, E. I., Luong, R. H., Baker, J. B., Zeiser, R., & Negrin, R. S. (2011) · Blood · doi:10.1182/blood-2010-08-303008 · Cited by 119
Self-citation
Immunogenicity assessment of AAV-based gene therapies: An IQ consortium industry white paper
Yang, T., Braun, M., Lembke, W., McBlane, F., Kamerud, J., DeWall, S. L., Tarcsa, E., Fang, X., Hofer, L., Kavita, U., et al. (2022) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2022.07.018 · Cited by 122
CD4+ invariant natural killer T cells protect from murine GVHD lethality through expansion of donor CD4+CD25+FoxP3+ regulatory T cells
Schneidawind, D., Pierini, A., Álvarez, M., Pan, Y., Baker, J. B., Buechele, C., Luong, R. H., Meyer, E. H., & Negrin, R. S. (2014) · Blood · doi:10.1182/blood-2014-05-576017 · Cited by 115
Self-citation
Mechanistic approaches for the prevention and treatment of chronic GVHD
Cutler, C. S., Koreth, J., & Ritz, J. (2016) · Blood · doi:10.1182/blood-2016-08-686659 · Cited by 118
Sirolimus as Primary Immunosuppression Attenuates Allograft Vasculopathy With Improved Late Survival and Decreased Cardiac Events After Cardiac Transplantation
Topilsky, Y., Hasin, T., Raichlin, E., Boilson, B. A., Schirger, J. A., Pereira, N. L., Edwards, B. S., Clavell, A. L., Rodeheffer, R. J., Frantz, R. P., et al. (2011) · Circulation · doi:10.1161/circulationaha.111.040360 · Cited by 113
Pathogenesis of acute graft‐versus‐host disease: from intestinal microbiota alterations to donor T cell activation
Zeiser, R., Socié, G., & Blazar, B. R. (2016) · British Journal of Haematology · doi:10.1111/bjh.14295 · Cited by 117
Self-citation
AKT isoforms modulate Th1‐like Treg generation and function in human autoimmune disease
Kitz, A., de Marcken, M., Gautron, A.-S., Mitrovič, M., Hafler, D. A., & Dominguez‐Villar, M. (2016) · EMBO Reports · doi:10.15252/embr.201541905 · Cited by 110
Impact of age on T cell signaling: A general defect or specific alterations?
Larbi, A., Pawelec, G., Wong, S. C., Goldeck, D., Tai, J. J.-Y., & Fulop, T. (2011) · Ageing Research Reviews · doi:10.1016/j.arr.2010.09.008 · Cited by 108
Ex Vivo–Expanded but Not In Vitro–Induced Human Regulatory T Cells Are Candidates for Cell Therapy in Autoimmune Diseases Thanks to Stable Demethylation of the FOXP3 Regulatory T Cell–Specific Demethylated Region
Rossetti, M. M., Spreafico, R., Saidin, S., Chua, C. J. H., Moshref, M., Leong, J. Y., Tan, Y. K., Thumboo, J., van Loosdregt, J., & Albani, S. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1401145 · Cited by 109
New Insights on OX40 in the Control of T Cell Immunity and Immune Tolerance In Vivo
Xiao, X., Gong, W., Demirci, G., Liu, W., Spoerl, S., Chu, X., Bishop, D. K., Turka, L. A., & Li, X. C. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1101373 · Cited by 102
Methods to manufacture regulatory T cells for cell therapy
MacDonald, K. N., Piret, J. M., & Levings, M. K. (2019) · Clinical & Experimental Immunology · doi:10.1111/cei.13297 · Cited by 103
The emerging role of anti‐ CD 25 directed therapies as both immune modulators and targeted agents in cancer
Flynn, M. J., & Hartley, J. A. (2017) · British Journal of Haematology · doi:10.1111/bjh.14770 · Cited by 99
A randomized phase II study to evaluate tacrolimus in combination with sirolimus or methotrexate after allogeneic hematopoietic cell transplantation
Pidala, J., Kim, J., Jim, H., Kharfan‐Dabaja, M. A., Nishihori, T., Fernandez, H. F., Tomblyn, M. R., Perez, L. E., Perkins, J. B., Xu, M., et al. (2012) · Haematologica · doi:10.3324/haematol.2012.067140 · Cited by 98
Multiparameter Flow Cytometry: Advances in High Resolution Analysis
O'Donnell, E. A., Ernst, D. N., & Hingorani, R. (2013) · Immune Network · doi:10.4110/in.2013.13.2.43 · Cited by 95
Mammalian Target of Rapamycin Inhibition and Alloantigen-Specific Regulatory T Cells Synergize To Promote Long-Term Graft Survival in Immunocompetent Recipients
Raimondi, G., Sumpter, T. L., Matta, B. M., Pillai, M., Corbitt, N., Yoram Vodovotz, B., Wang, Z., & Thomson, A. W. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0900936 · Cited by 96
Regulatory T cells for tolerance
Kawai, K., Uchiyama, M., Hester, J., Wood, K. J., & Issa, F. (2017) · Human Immunology · doi:10.1016/j.humimm.2017.12.013 · Cited by 99
Future prospects for CD8+ regulatory T cells in immune tolerance
Flippe, L., Bézie, S., Anegón, I., & Guillonneau, C. (2019) · Immunological Reviews · doi:10.1111/imr.12812 · Cited by 98
Graft-versus-host disease prophylaxis: Pathophysiology-based review on current approaches and future directions
Martínez‐Cibrián, N., Zeiser, R., & Pérez‐Simón, J. A. (2020) · Blood Reviews · doi:10.1016/j.blre.2020.100792 · Cited by 97
Self-citation
The Role of Mechanistic Target of Rapamycin (mTOR) Complexes Signaling in the Immune Responses
Soliman, G. A. (2013) · Nutrients · doi:10.3390/nu5062231 · Cited by 97
Low-Dose Rapamycin Treatment Increases the Ability of Human Regulatory T Cells to Inhibit Transplant Arteriosclerosis In Vivo
Hester, J., Șchiopu, A., Nadig, S. N., & Wood, K. J. (2012) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2012.04065.x · Cited by 92
The therapeutic potential of regulatory T cells for the treatment of autoimmune disease
Bluestone, J. A., Trotta, E., & Xu, D. (2015) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2015.1037282 · Cited by 96
Advances in understanding the pathogenesis of graft‐versus‐host disease
Zeiser, R. (2019) · British Journal of Haematology · doi:10.1111/bjh.16190 · Cited by 91
Self-citation
Induction of tolerance to factor VIII by transient co‐administration with rapamycin
Moghimi, B., Sack, B. K., Nayak, S., Markusic, D. M., Mah, C. S., & Herzog, R. W. (2011) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2011.04351.x · Cited by 91
Deficiency of CD73/ecto-5′-nucleotidase in mice enhances acute graft-versus-host disease
Tsukamoto, H., Chernogorova, P., Ayata, C. K., Gerlach, U. V., Rughani, A., Ritchey, J. W., Ganesan, J., Follo, M., Zeiser, R., Thompson, L. F., et al. (2012) · Blood · doi:10.1182/blood-2011-09-375899 · Cited by 91
Self-citation
Third-party CD4+ invariant natural killer T cells protect from murine GVHD lethality
Schneidawind, D., Baker, J. B., Pierini, A., Buechele, C., Luong, R. H., Meyer, E. H., & Negrin, R. S. (2015) · Blood · doi:10.1182/blood-2014-11-612762 · Cited by 91
Self-citation
Induced regulatory T cells in inhibitory microenvironments created by cancer
Whiteside, T. L. (2014) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.2014.927432 · Cited by 97
Regulatory T cells and natural killer T cells for modulation of GVHD following allogeneic hematopoietic cell transplantation
Schneidawind, D., Pierini, A., & Negrin, R. S. (2013) · Blood · doi:10.1182/blood-2013-08-453126 · Cited by 88
Self-citation
Pharmacotherapy for uveitis: current management and emerging therapy
Denniston, A. K., Barry, R. J., Nguyen, Q. D., Lee, R., & Murray, P. I. (2014) · Clinical ophthalmology · doi:10.2147/opth.s47778 · Cited by 86
Impact of Mammalian Target of Rapamycin Inhibition on Lymphoid Homing and Tolerogenic Function of Nanoparticle-Labeled Dendritic Cells following Allogeneic Hematopoietic Cell Transplantation
Reichardt, W., Dürr, C., von Elverfeldt, D., Jüttner, E., Gerlach, U. V., Yamada, M., Smith, B., Negrin, R. S., & Zeiser, R. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.7.4770 · Cited by 88
Self-citation
Preclinical models of acute and chronic graft-versus-host disease: how predictive are they for a successful clinical translation?
Zeiser, R., & Blazar, B. R. (2016) · Blood · doi:10.1182/blood-2016-02-699082 · Cited by 84
Self-citation
TSLP directly impairs pulmonary Treg function: association with aberrant tolerogenic immunity in asthmatic airway
Nguyen, K. D., Vanichsarn, C. T., & Nadeau, K. C. (2010) · Allergy Asthma and Clinical Immunology · doi:10.1186/1710-1492-6-4 · Cited by 84
Immune Regulatory Cells in Umbilical Cord Blood and Their Potential Roles in Transplantation Tolerance
Kim, Y.-J., & Broxmeyer, H. (2010) · Critical reviews in oncology/hematology · doi:10.1016/j.critrevonc.2010.07.009 · Cited by 71
Immune dysregulation in patients with PTEN hamartoma tumor syndrome: Analysis of FOXP3 regulatory T cells
Chen, H. H., Händel, N., Ngeow, J. Y. Y., Muller, J., Hühn, M. H., Yang, H.-T., Heindl, M., Berbers, R.-M., Hegazy, A. N., Kionke, J., et al. (2016) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2016.03.059 · Cited by 75
Follicular lymphoma B cells induce the conversion of conventional CD4+ T cells to T‐regulatory cells
Ai, W. Z., Hou, J., Zeiser, R., Czerwinski, D. K., Negrin, R. S., & Levy, R. (2008) · International Journal of Cancer · doi:10.1002/ijc.23881 · Cited by 75
Self-citation
Lactic acid bacteria-specific induction of CD4+Foxp3+T cells ameliorates shrimp tropomyosin-induced allergic response in mice via suppression of mTOR signaling
Fu, L., Peng, J., Zhao, S., Zhang, Y., Su, X., & Wang, Y. (2017) · Scientific Reports · doi:10.1038/s41598-017-02260-8 · Cited by 76
Selective expansion of regulatory T cells using an orthogonal IL-2/IL-2 receptor system facilitates transplantation tolerance
Hirai, T., Ramos, T. L., Lin, P., Simonetta, F., Su, L., Picton, L. K., Baker, J. B., Lin, J., Li, P., Seo, K., et al. (2021) · Journal of Clinical Investigation · doi:10.1172/jci139991 · Cited by 72
Self-citation
Regulatory T Cells (Tregs) and COVID-19: Unveiling the Mechanisms, and Therapeutic Potentialities with a Special Focus on Long COVID
Dhawan, M. K., Rabaan, A. A., Alwarthan, S. M., Alhajri, M. M., Halwani, M. A., Alshengeti, A., Najim, M. A., Alwashmi, A. S. S., Alshehri, A. A., Alshamrani, S., et al. (2023) · Vaccines · doi:10.3390/vaccines11030699 · Cited by 79
Subsets of human CD4 + regulatory T cells express the peripheral homing receptor CXCR3
Hoerning, A., Koss, K. E., Datta, D. B., Boneschansker, L., Jones, C. N., Wong, I. Y., Irimia, D., Calzadilla, K., Benítez, F., Hoyer, P. F., et al. (2011) · European Journal of Immunology · doi:10.1002/eji.201041095 · Cited by 73
Superiority of Rapamycin Over Tacrolimus in Preserving Nonhuman Primate Treg Half-Life and Phenotype After Adoptive Transfer
Singh, K., Stempora, L., Harvey, R. D., Kirk, A. D., Larsen, C. P., Blazar, B. R., & Kean, L. S. (2014) · American Journal of Transplantation · doi:10.1111/ajt.12934 · Cited by 70
Synergy between rapamycin and FLT3 ligand enhances plasmacytoid dendritic cell-dependent induction of CD4+CD25+FoxP3+ Treg
Biswas, M., Sarkar, D., Kumar, S. R. P., Nayak, S., Rogers, G. L., Markusic, D. M., Liao, G., Terhorst, C., & Herzog, R. W. (2015) · Blood · doi:10.1182/blood-2014-09-599266 · Cited by 70
A TNFR2-Agonist Facilitates High Purity Expansion of Human Low Purity Treg Cells
He, X., Landman, S., Bauland, S. C. G., van den Dolder, J., Koenen, H. J. P. M., & Joosten, I. (2016) · PLoS ONE · doi:10.1371/journal.pone.0156311 · Cited by 69
Stable human regulatory T cells switch to glycolysis following TNF receptor 2 costimulation
de Kivit, S., Mensink, M., Hoekstra, A. T., Berlin, I., Derks, R. J. E., Both, D., Aslam, M. A., Amsen, D., Berkers, C. R., & Borst, J. G. (2020) · Nature Metabolism · doi:10.1038/s42255-020-00271-w · Cited by 69
Prophylactic immune tolerance induced by changing the ratio of antigen-specific effector to regulatory T cells
NAYAK, S., CAO, O., HOFFMAN, B. E., COOPER, M., ZHOU, S., ATKINSON, M. A., & HERZOG, R. W. (2009) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2009.03548.x · Cited by 66
Intracellular metabolic pathways control immune tolerance
Procaccini, C., Galgani, M., Rosa, V. D., & Matarese, G. (2011) · Trends in Immunology · doi:10.1016/j.it.2011.09.002 · Cited by 67
A DAP5/eIF3d alternate mRNA translation mechanism promotes differentiation and immune suppression by human regulatory T cells
Volta, V., Pérez-Baos, S., de la Parra, C., Katsara, O., Ernlund, A. W., Dornbaum, S., & Schneider, R. J. (2021) · Nature Communications · doi:10.1038/s41467-021-27087-w · Cited by 64
Regulatory T cells: tolerance induction in solid organ transplantation
Vaikunthanathan, T., Safinia, N., Boardman, D. A., Lechler, R. I., & Lombardi, G. (2017) · Clinical & Experimental Immunology · doi:10.1111/cei.12978 · Cited by 65

Authors: Zeiser, R., Leveson-Gower, D. B., Zambricki, E. A., Kambham, N., Beilhack, A., Loh, J., Hou, J.-Z., & Negrin, R. S.
Affiliations: University of Freiburg (DE)
Stanford Medicine (US)
ORCID: Zeiser, Robert
Kambham, Neeraja
Beilhack, Andreas
Hou, Jing-Zhou
Negrin, Robert S.
Venue: Blood
Publisher: American Society of Hematology
Published: 2008-01-01
Volume: 111
Issue: 1
Pages: 453-462
ISSN: 0006-4971 (ISSN-L)
1528-0020
DOI: 10.1182/blood-2007-06-094482
PMC: PMC2200823
OpenAlex: W1981298448
Cited by: 402
References: 52
Citations by year: 2026: 10 · 2025: 8 · 2024: 9 · 2023: 17 · 2022: 9 · 2021: 21 · 2020: 17 · 2019: 21 · 2018: 23 · 2017: 18 · 2016: 31 · 2015: 24 · 2014: 33 · 2013: 27 · 2012: 32
FWCI: 8.68
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Blood (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Deutsche Krebshilfe
National Institutes of Health (HL075462)
National Heart, Lung, and Blood Institute (P01HL075462)
National Cancer Institute (P50CA114747, R01 CA0800065, HL075462, R24 CA 92862, R24CA092862)
Topics: Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
Health Sciences › Medicine › Transplantation › Renal Transplantation Outcomes and Treatments
Keywords: regulatory T cells, mTOR inhibition, rapamycin, acute graft-versus-host disease, conventional CD4+ T cells, STAT5 phosphorylation, PI3K/AKT/mTOR pathway, PTEN, Foxp3, interleukin-2, Treg therapy
MeSH terms: Animals, Graft vs Host Disease, Immunosuppressive Agents, Mice, Inbred BALB C, Mice, Inbred C57BL, Protein Kinases, CD4-Positive T-Lymphocytes, Hematopoietic Stem Cell Transplantation, Phosphatidylinositol 3-Kinases, Sirolimus, T-Lymphocytes, Regulatory, STAT5 Transcription Factor, Proto-Oncogene Proteins c-akt, PTEN Phosphohydrolase, Mice, Forkhead Transcription Factors, Interleukin-2 Receptor alpha Subunit, TOR Serine-Threonine Kinases

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Differential impact of mammalian target of rapamycin inhibition on CD4 +CD25+Foxp3+ regulatory T cells compared with conventional CD4+ T cells

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks