Regulatory T Cells Negatively Affect IL-2 Production of Effector T Cells through CD39/Adenosine Pathway in HIV Infection

The mechanisms by which Regulatory T cells suppress IL-2 production of effector CD4+ T cells in pathological conditions are unclear. A subpopulation of human Treg expresses the ectoenzyme CD39, which in association with CD73 converts ATP/ADP/AMP to adenosine. We show here that Treg/CD39+ suppress IL...

Full description

Saved in:
Bibliographic Details
Published inPLoS pathogens Vol. 9; no. 4; p. e1003319
Main Authors Jenabian, Mohammad-Ali, Seddiki, Nabila, Yatim, Ahmad, Carriere, Matthieu, Hulin, Anne, Younas, Mehwish, Ghadimi, Elnaz, Kök, Ayrin, Routy, Jean-Pierre, Tremblay, Alain, Sévigny, Jean, Lelievre, Jean-Daniel, Levy, Yves
Format Journal Article
LanguageEnglish
Published United States Public Library of Science 01.04.2013
Public Library of Science (PLoS)
Subjects
5'-Nucleotidase - metabolism
Adenosine
Adenosine - metabolism
Antibodies, Monoclonal - immunology
Antigens, CD - biosynthesis
Antigens, CD - immunology
Antigens, CD - metabolism
Apyrase - biosynthesis
Apyrase - immunology
Apyrase - metabolism
Biology
Cell Proliferation
Cyclic AMP - metabolism
DNA Methylation
Health aspects
HIV
HIV infection
HIV Infections - immunology
HIV-1 - immunology
Host-parasite relationships
Human immunodeficiency virus
Humans
Immune system
Interleukin-2
Interleukin-2 - biosynthesis
Interleukin-2 - genetics
Lymphocyte Activation
Medical research
Medicine
Physiological aspects
Promoter Regions, Genetic
Proteins
Receptor, Adenosine A2A - metabolism
T cell receptors
T cells
T-Lymphocyte Subsets - immunology
T-Lymphocyte Subsets - metabolism
T-Lymphocytes, Regulatory - immunology
T-Lymphocytes, Regulatory - metabolism
France
Canada
Online AccessGet full text

Cover

Abstract The mechanisms by which Regulatory T cells suppress IL-2 production of effector CD4+ T cells in pathological conditions are unclear. A subpopulation of human Treg expresses the ectoenzyme CD39, which in association with CD73 converts ATP/ADP/AMP to adenosine. We show here that Treg/CD39+ suppress IL-2 expression of activated CD4+ T-cells more efficiently than Treg/CD39-. This inhibition is due to the demethylation of an essential CpG site of the il-2 gene promoter, which was reversed by an anti-CD39 mAb. By recapitulating the events downstream CD39/adenosine receptor (A2AR) axis, we show that A2AR agonist and soluble cAMP inhibit CpG site demethylation of the il-2 gene promoter. A high frequency of Treg/CD39+ is associated with a low clinical outcome in HIV infection. We show here that CD4+ T-cells from HIV-1 infected individuals express high levels of A2AR and intracellular cAMP. Following in vitro stimulation, these cells exhibit a lower degree of demethylation of il-2 gene promoter associated with a lower expression of IL-2, compared to healthy individuals. These results extend previous data on the role of Treg in HIV infection by filling the gap between expansion of Treg/CD39+ in HIV infection and the suppression of CD4+ T-cell function through inhibition of IL-2 production.
AbstractList The mechanisms by which Regulatory T cells suppress IL-2 production of effector CD4+ T cells in pathological conditions are unclear. A subpopulation of human Treg expresses the ectoenzyme CD39, which in association with CD73 converts ATP/ADP/AMP to adenosine. We show here that Treg/CD39+ suppress IL-2 expression of activated CD4+ T-cells more efficiently than Treg/CD39−. This inhibition is due to the demethylation of an essential CpG site of the il-2 gene promoter, which was reversed by an anti-CD39 mAb. By recapitulating the events downstream CD39/adenosine receptor (A2AR) axis, we show that A2AR agonist and soluble cAMP inhibit CpG site demethylation of the il-2 gene promoter. A high frequency of Treg/CD39+ is associated with a low clinical outcome in HIV infection. We show here that CD4+ T-cells from HIV-1 infected individuals express high levels of A2AR and intracellular cAMP. Following in vitro stimulation, these cells exhibit a lower degree of demethylation of il-2 gene promoter associated with a lower expression of IL-2, compared to healthy individuals. These results extend previous data on the role of Treg in HIV infection by filling the gap between expansion of Treg/CD39+ in HIV infection and the suppression of CD4+ T-cell function through inhibition of IL-2 production. Regulatory T cells (Treg) represent a subset of T lymphocytes and have a pivotal role in chronic viral infections and cancer by limiting immune activation. It has been shown that Treg are expanded in chronic HIV infected patients. However, the mechanisms of Treg immune-modulator functions are not clearly known. CD39 is an ectonucleotidase which converts the proinflammatory ATP signal into AMP and the immunosuppressive adenosine in concert with another ecto-enzyme CD73. We have previously reported that CD39/adenosine pathway is involved in AIDS progression. However, the mechanism of Treg immunosuppression through CD39 and its involvement in HIV pathogenesis remains unclear. We report here that Treg/CD39+ inhibits the production of IL-2, a cytokine that stimulates the growth of T lymphocytes, via CD39/Adenosine/cAMP enzymatic pathway. The signals induced by adenosine specific receptor A2AR, increase the intra cellular levels of cAMP. We show that cAMP inhibits CpG site demethylation of the il-2 gene promoter. We found that T cells from HIV patients have a higher expression on A2AR as well as intra-cellular cAMP and a lesser capacity to produce IL-2 upon stimulation than healthy subjects. Our results contribute to elucidate the mechanisms by which Treg suppression occurs during HIV infection.
The mechanisms by which Regulatory T cells suppress IL-2 production of effector CD4+ T cells in pathological conditions are unclear. A subpopulation of human Treg expresses the ectoenzyme CD39, which in association with CD73 converts ATP/ADP/AMP to adenosine. We show here that Treg/CD39+ suppress IL-2 expression of activated CD4+ T-cells more efficiently than Treg/CD39-. This inhibition is due to the demethylation of an essential CpG site of the il-2 gene promoter, which was reversed by an anti-CD39 mAb. By recapitulating the events downstream CD39/adenosine receptor (A2AR) axis, we show that A2AR agonist and soluble cAMP inhibit CpG site demethylation of the il-2 gene promoter. A high frequency of Treg/CD39+ is associated with a low clinical outcome in HIV infection. We show here that CD4+ T-cells from HIV-1 infected individuals express high levels of A2AR and intracellular cAMP. Following in vitro stimulation, these cells exhibit a lower degree of demethylation of il-2 gene promoter associated with a lower expression of IL-2, compared to healthy individuals. These results extend previous data on the role of Treg in HIV infection by filling the gap between expansion of Treg/CD39+ in HIV infection and the suppression of CD4+ T-cell function through inhibition of IL-2 production.
  The mechanisms by which Regulatory T cells suppress IL-2 production of effector CD4+ T cells in pathological conditions are unclear. A subpopulation of human Treg expresses the ectoenzyme CD39, which in association with CD73 converts ATP/ADP/AMP to adenosine. We show here that Treg/CD39+ suppress IL-2 expression of activated CD4+ T-cells more efficiently than Treg/CD39-. This inhibition is due to the demethylation of an essential CpG site of the il-2 gene promoter, which was reversed by an anti-CD39 mAb. By recapitulating the events downstream CD39/adenosine receptor (A2AR) axis, we show that A2AR agonist and soluble cAMP inhibit CpG site demethylation of the il-2 gene promoter. A high frequency of Treg/CD39+ is associated with a low clinical outcome in HIV infection. We show here that CD4+ T-cells from HIV-1 infected individuals express high levels of A2AR and intracellular cAMP. Following in vitro stimulation, these cells exhibit a lower degree of demethylation of il-2 gene promoter associated with a lower expression of IL-2, compared to healthy individuals. These results extend previous data on the role of Treg in HIV infection by filling the gap between expansion of Treg/CD39+ in HIV infection and the suppression of CD4+ T-cell function through inhibition of IL-2 production.
The mechanisms by which Regulatory T cells suppress IL-2 production of effector CD4+ T cells in pathological conditions are unclear. A subpopulation of human Treg expresses the ectoenzyme CD39, which in association with CD73 converts ATP/ADP/AMP to adenosine. We show here that Treg/CD39+ suppress IL-2 expression of activated CD4+ T-cells more efficiently than Treg/CD39-. This inhibition is due to the demethylation of an essential CpG site of the il-2 gene promoter, which was reversed by an anti-CD39 mAb. By recapitulating the events downstream CD39/adenosine receptor (A2AR) axis, we show that A2AR agonist and soluble cAMP inhibit CpG site demethylation of the il-2 gene promoter. A high frequency of Treg/CD39+ is associated with a low clinical outcome in HIV infection. We show here that CD4+ T-cells from HIV-1 infected individuals express high levels of A2AR and intracellular cAMP. Following in vitro stimulation, these cells exhibit a lower degree of demethylation of il-2 gene promoter associated with a lower expression of IL-2, compared to healthy individuals. These results extend previous data on the role of Treg in HIV infection by filling the gap between expansion of Treg/CD39+ in HIV infection and the suppression of CD4+ T-cell function through inhibition of IL-2 production.The mechanisms by which Regulatory T cells suppress IL-2 production of effector CD4+ T cells in pathological conditions are unclear. A subpopulation of human Treg expresses the ectoenzyme CD39, which in association with CD73 converts ATP/ADP/AMP to adenosine. We show here that Treg/CD39+ suppress IL-2 expression of activated CD4+ T-cells more efficiently than Treg/CD39-. This inhibition is due to the demethylation of an essential CpG site of the il-2 gene promoter, which was reversed by an anti-CD39 mAb. By recapitulating the events downstream CD39/adenosine receptor (A2AR) axis, we show that A2AR agonist and soluble cAMP inhibit CpG site demethylation of the il-2 gene promoter. A high frequency of Treg/CD39+ is associated with a low clinical outcome in HIV infection. We show here that CD4+ T-cells from HIV-1 infected individuals express high levels of A2AR and intracellular cAMP. Following in vitro stimulation, these cells exhibit a lower degree of demethylation of il-2 gene promoter associated with a lower expression of IL-2, compared to healthy individuals. These results extend previous data on the role of Treg in HIV infection by filling the gap between expansion of Treg/CD39+ in HIV infection and the suppression of CD4+ T-cell function through inhibition of IL-2 production.
Audience Academic
Author Younas, Mehwish
Ghadimi, Elnaz
Lelievre, Jean-Daniel
Jenabian, Mohammad-Ali
Sévigny, Jean
Yatim, Ahmad
Tremblay, Alain
Routy, Jean-Pierre
Kök, Ayrin
Levy, Yves
Carriere, Matthieu
Seddiki, Nabila
Hulin, Anne
AuthorAffiliation 6 Division of Hematology and Chronic Viral Illness Service, McGill University Health Centre, Montreal, Québec, Canada
8 Groupe Henri-Mondor Albert-Chènevière, Immunologie Clinique, Créteil, France
4 Groupe Henri-Mondor Albert-Chènevière, Laboratory of Pharmacology and Toxicology, Créteil, France
2 Faculté de Médecine, Université Paris Est Créteil, Créteil, France
3 Vaccine Research Institute, Agence Nationale de Recherche sur le Sida et les hépatites virales (ANRS) HIV Vaccine Network (AHVN), Créteil, France
1 INSERM U955, Equipe 16, Créteil, France
National Institute of Allergy and Infectious Diseases, National Institutes of Health, United States of America
5 Faculty of Dentistry, McGill University, Montréal, Québec, Canada
7 Centre de Recherche en Rhumatologie et Immunologie, Centre de Recherche du CHU de Québec, and Département de Microbiologie-Infectiologie et d'Immunologie, Faculté de Médecine, Université Laval, Québec, Québec, Canada
AuthorAffiliation_xml – name: 6 Division of Hematology and Chronic Viral Illness Service, McGill University Health Centre, Montreal, Québec, Canada
– name: 8 Groupe Henri-Mondor Albert-Chènevière, Immunologie Clinique, Créteil, France
– name: 4 Groupe Henri-Mondor Albert-Chènevière, Laboratory of Pharmacology and Toxicology, Créteil, France
– name: 7 Centre de Recherche en Rhumatologie et Immunologie, Centre de Recherche du CHU de Québec, and Département de Microbiologie-Infectiologie et d'Immunologie, Faculté de Médecine, Université Laval, Québec, Québec, Canada
– name: 1 INSERM U955, Equipe 16, Créteil, France
– name: 2 Faculté de Médecine, Université Paris Est Créteil, Créteil, France
– name: National Institute of Allergy and Infectious Diseases, National Institutes of Health, United States of America
– name: 5 Faculty of Dentistry, McGill University, Montréal, Québec, Canada
– name: 3 Vaccine Research Institute, Agence Nationale de Recherche sur le Sida et les hépatites virales (ANRS) HIV Vaccine Network (AHVN), Créteil, France
Author_xml – sequence: 1
  givenname: Mohammad-Ali
  surname: Jenabian
  fullname: Jenabian, Mohammad-Ali
– sequence: 2
  givenname: Nabila
  surname: Seddiki
  fullname: Seddiki, Nabila
– sequence: 3
  givenname: Ahmad
  surname: Yatim
  fullname: Yatim, Ahmad
– sequence: 4
  givenname: Matthieu
  surname: Carriere
  fullname: Carriere, Matthieu
– sequence: 5
  givenname: Anne
  surname: Hulin
  fullname: Hulin, Anne
– sequence: 6
  givenname: Mehwish
  surname: Younas
  fullname: Younas, Mehwish
– sequence: 7
  givenname: Elnaz
  surname: Ghadimi
  fullname: Ghadimi, Elnaz
– sequence: 8
  givenname: Ayrin
  surname: Kök
  fullname: Kök, Ayrin
– sequence: 9
  givenname: Jean-Pierre
  surname: Routy
  fullname: Routy, Jean-Pierre
– sequence: 10
  givenname: Alain
  surname: Tremblay
  fullname: Tremblay, Alain
– sequence: 11
  givenname: Jean
  surname: Sévigny
  fullname: Sévigny, Jean
– sequence: 12
  givenname: Jean-Daniel
  surname: Lelievre
  fullname: Lelievre, Jean-Daniel
– sequence: 13
  givenname: Yves
  surname: Levy
  fullname: Levy, Yves
BackLink https://www.ncbi.nlm.nih.gov/pubmed/23658513$$D View this record in MEDLINE/PubMed
BookMark eNqVkl1v0zAUhiM0xD7gHyCwxA1ctLPjjyRcIFVlsErVmEbFreXEduoqtYvtjPXf435NK0JIyBd2jp_3zdHxe56dWGdVlr1GcIhwgS4XrvdWdMPVSsQhghBjVD3LzhCleFDggpw8OZ9m5yEsICQII_YiO80xoyVF-Cx7uFNt34no_BrMwFh1XQA3qhXR3KtuDUZaqyaCyXSQg1vvZN9E4yxwGlxtb5x_VMW5d307B-PPuLocSWVdMFaBWxHnv8QaGAuuJz_AxG5kyeNl9lyLLqhX-_0im325mo2vB9NvXyfj0XTQMIzjgBIlSliUAtWQ0ZpoJFWZo7IWMNWhlkqXTDNJa6Yxqgmta4VE-qCUwVzii-ztznbVucD3MwscYYrKqiA5TcRkR0gnFnzlzVL4NXfC8G3B-ZYLH03TKS5zClEhiCSYEUJ1xShWZaGbSiAm8zx5fdr_ra-XSjbKRi-6I9PjG2vmvHX3HDNMqwImg_d7A-9-9ipEvjShSfMVVrl-2zdENCeoSOi7HdqK1Jqx2iXHZoPzEcaQVGVFWKKGf6HSkmppmpQobVL9SPDhSJCYqB5iK_oQ-OT73X-wN8fsm6ejeZzJIYoJ-LgDGu9C8ErzxkSxiUrq2HQcQb7J_eEN-Sb3fJ_7JCZ_iA_-_5T9BmtUBrw
CitedBy_id crossref_primary_10_1186_s40425_014_0038_9
crossref_primary_10_3389_fimmu_2022_904419
crossref_primary_10_4137_IJTR_S38355
crossref_primary_10_1136_bmjopen_2018_024793
crossref_primary_10_1111_ajd_12561
crossref_primary_10_3389_fimmu_2025_1536020
crossref_primary_10_3389_fimmu_2022_869286
crossref_primary_10_1128_JVI_00371_19
crossref_primary_10_1093_infdis_jiu549
crossref_primary_10_1007_s11302_021_09838_y
crossref_primary_10_1002_biot_202300446
crossref_primary_10_1371_journal_ppat_1006489
crossref_primary_10_1016_j_jim_2016_02_004
crossref_primary_10_3390_cells12141811
crossref_primary_10_1038_nri_2016_4
crossref_primary_10_1089_aid_2019_0134
crossref_primary_10_1016_j_trim_2021_101411
crossref_primary_10_1002_1873_3468_12849
crossref_primary_10_1016_j_cellimm_2014_07_005
crossref_primary_10_1016_j_meegid_2018_05_001
crossref_primary_10_1007_s11302_018_9619_2
crossref_primary_10_1186_s13046_020_01546_6
crossref_primary_10_1186_s13045_024_01524_x
crossref_primary_10_1371_journal_pone_0116575
crossref_primary_10_3389_fimmu_2021_687296
crossref_primary_10_3390_pathogens12020279
crossref_primary_10_1371_journal_ppat_1012191
crossref_primary_10_1007_s11302_021_09817_3
crossref_primary_10_1097_QAI_0b013e3182a4b9ad
crossref_primary_10_1002_stem_1934
crossref_primary_10_1016_j_cytogfr_2023_01_001
crossref_primary_10_1099_jgv_0_000260
crossref_primary_10_3389_fimmu_2022_962912
crossref_primary_10_1093_infdis_jix547
crossref_primary_10_1371_journal_pone_0078146
crossref_primary_10_3389_fimmu_2016_00216
crossref_primary_10_1128_jvi_00255_22
crossref_primary_10_3390_ijms19123837
crossref_primary_10_3389_fimmu_2022_867167
crossref_primary_10_1189_jlb_5A0816_346R
crossref_primary_10_1016_j_lfs_2021_119132
crossref_primary_10_1016_S2055_6640_20_30684_1
crossref_primary_10_1089_aid_2015_0151
crossref_primary_10_3390_v16101609
crossref_primary_10_1128_JVI_01196_15
crossref_primary_10_1128_JVI_01788_20
crossref_primary_10_1016_j_molimm_2014_09_015
crossref_primary_10_1016_j_yjmcc_2019_01_005
crossref_primary_10_1371_journal_ppat_1006745
crossref_primary_10_1093_ofid_ofab396
crossref_primary_10_1097_QAD_0000000000002842
crossref_primary_10_1371_journal_pone_0098745
crossref_primary_10_1371_journal_ppat_1005177
crossref_primary_10_1007_s00262_013_1490_y
crossref_primary_10_1016_j_humimm_2016_02_005
crossref_primary_10_1189_jlb_3A1214_580RR
crossref_primary_10_1186_s41231_019_0033_8
crossref_primary_10_3389_fimmu_2019_02465
crossref_primary_10_1093_infdis_jit643
crossref_primary_10_1158_2159_8290_CD_15_0447
crossref_primary_10_3389_fmicb_2023_1217801
crossref_primary_10_1097_QAD_0000000000001962
crossref_primary_10_1371_journal_ppat_1006776
crossref_primary_10_1007_s11033_024_09839_1
crossref_primary_10_3389_fimmu_2023_1201632
crossref_primary_10_1182_blood_2014_04_566786
crossref_primary_10_51758_AGJSR_04_2021_0033
crossref_primary_10_1016_j_ebiom_2021_103570
crossref_primary_10_1097_QAD_0000000000001282
Cites_doi 10.1074/jbc.M111.299339
10.1007/s11302-005-6217-x
10.1084/jem.20032069
10.1128/JVI.05608-11
10.1038/nm0804-801
10.1084/jem.20031598
10.1371/journal.ppat.1002110
10.1152/ajpgi.00165.2011
10.1084/jem.20062512
10.1097/QAD.0b013e328319edc0
10.1084/jem.20062129
10.1146/annurev.immunol.22.012703.104731
10.1158/0008-5472.CAN-09-3109
10.1074/jbc.271.51.33116
10.1097/QAD.0b013e3282f466da
10.1371/journal.pone.0015924
10.1111/j.1399-0039.1990.tb01750.x
10.1182/blood-2004-01-0365
10.1038/ni1181
10.1016/0008-8749(88)90164-5
10.1182/blood-2009-11-252668
10.4049/jimmunol.180.9.5916
10.1084/jem.20060468
10.1182/blood-2004-04-1407
10.1016/B978-0-12-385526-8.00009-6
10.1089/aid.2011.0265
10.1182/blood-2010-12-323162
10.1056/NEJMe1110900
10.1016/0167-5699(88)91220-0
10.1086/596205
10.1128/JVI.01758-10
10.1038/nri2343
10.1096/fasebj.12.10.855
10.1038/sj.bjp.0703136
10.1182/blood.V90.4.1600
10.4049/jimmunol.0901247
10.1016/j.coi.2004.01.004
10.1084/jem.20060772
10.1038/414916a
10.1016/S0026-895X(25)10033-3
10.1074/jbc.M111.299313
10.1016/j.thromres.2007.04.008
10.4049/jimmunol.165.4.1755
10.4049/jimmunol.172.10.5986
10.1016/j.bbamcr.2005.10.009
10.1128/JVI.72.6.4712-4720.1998
10.4049/jimmunol.1102045
10.1084/jem.20030891
10.1034/j.1600-065X.2001.1820117.x
10.1128/JVI.78.5.2454-2459.2004
10.1371/journal.pone.0040829
10.1097/COH.0b013e3283454058
10.1038/sj.emboj.7601012
10.1182/blood-2006-12-064527
10.1002/eji.200838667
10.1016/j.imlet.2010.01.007
10.1158/0008-5472.CAN-10-1544
10.1158/1078-0432.CCR-09-1143
10.1083/jcb.136.2.421
10.4049/jimmunol.0902955
10.1096/fj.00-0813fje
10.1038/nri2785
10.1007/s11302-006-9050-y
ContentType Journal Article
Copyright COPYRIGHT 2013 Public Library of Science
2013 Jenabian et al 2013 Jenabian et al
2013 Jenabian et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Jenabian M-A, Seddiki N, Yatim A, Carriere M, Hulin A, et al. (2013) Regulatory T Cells Negatively Affect IL-2 Production of Effector T Cells through CD39/Adenosine Pathway in HIV Infection. PLoS Pathog 9(4): e1003319. doi:10.1371/journal.ppat.1003319
Copyright_xml – notice: COPYRIGHT 2013 Public Library of Science
– notice: 2013 Jenabian et al 2013 Jenabian et al
– notice: 2013 Jenabian et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Jenabian M-A, Seddiki N, Yatim A, Carriere M, Hulin A, et al. (2013) Regulatory T Cells Negatively Affect IL-2 Production of Effector T Cells through CD39/Adenosine Pathway in HIV Infection. PLoS Pathog 9(4): e1003319. doi:10.1371/journal.ppat.1003319
DBID AAYXX
CITATION
CGR
CUY
CVF
ECM
EIF
NPM
ISN
ISR
7X8
5PM
DOA
DOI 10.1371/journal.ppat.1003319
DatabaseName CrossRef
Medline
MEDLINE
MEDLINE (Ovid)
MEDLINE
MEDLINE
PubMed
Gale In Context: Canada
Gale In Context: Science
MEDLINE - Academic
PubMed Central (Full Participant titles)
Directory of Open Access Journals (DOAJ)
DatabaseTitle CrossRef
MEDLINE
Medline Complete
MEDLINE with Full Text
PubMed
MEDLINE (Ovid)
MEDLINE - Academic
DatabaseTitleList
MEDLINE



MEDLINE - Academic
Database_xml – sequence: 1
  dbid: DOA
  name: DOAJ Directory of Open Access Journals
  url: https://www.doaj.org/
  sourceTypes: Open Website
– sequence: 2
  dbid: NPM
  name: PubMed
  url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
  sourceTypes: Index Database
– sequence: 3
  dbid: EIF
  name: MEDLINE
  url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search
  sourceTypes: Index Database
DeliveryMethod fulltext_linktorsrc
Discipline Biology
Medicine
DocumentTitleAlternate Inhibition of IL-2 Expression by Treg via CD39
EISSN 1553-7374
ExternalDocumentID 1351897425
oai_doaj_org_article_d25017a4d436445f9653e87fc9a16d22
PMC3635970
A330498946
23658513
10_1371_journal_ppat_1003319
Genre Journal Article
GeographicLocations France
Canada
GeographicLocations_xml – name: Canada
– name: France
GroupedDBID ---
123
29O
2WC
53G
5VS
7X7
88E
8FE
8FH
8FI
8FJ
AAFWJ
AAUCC
AAWOE
AAYXX
ABDBF
ABUWG
ACGFO
ACIHN
ACPRK
ACUHS
ADBBV
ADRAZ
AEAQA
AENEX
AEUYN
AFKRA
AFPKN
AFRAH
AHMBA
ALMA_UNASSIGNED_HOLDINGS
AOIJS
B0M
BAWUL
BBNVY
BCNDV
BENPR
BHPHI
BPHCQ
BVXVI
BWKFM
CCPQU
CITATION
CS3
DIK
DU5
E3Z
EAP
EAS
EBD
EMK
EMOBN
ESX
F5P
FPL
FYUFA
GROUPED_DOAJ
GX1
HCIFZ
HMCUK
HYE
IAO
IHR
INH
INR
ISN
ISR
ITC
KQ8
LK8
M1P
M48
M7P
MM.
O5R
O5S
OK1
OVT
P2P
PGMZT
PHGZM
PHGZT
PIMPY
PJZUB
PPXIY
PQGLB
PQQKQ
PROAC
PSQYO
QF4
QN7
RNS
RPM
SV3
TR2
TUS
UKHRP
WOW
~8M
CGR
CUY
CVF
ECM
EIF
H13
IPNFZ
NPM
PV9
RIG
RZL
WOQ
PMFND
7X8
5PM
PUEGO
3V.
AAPBV
ABPTK
M~E
ID FETCH-LOGICAL-c633t-54ea8078a1b065b4f1de8218ba0a800fdef86f6d5b6f31b45bbe1ab6f55602d3
IEDL.DBID M48
ISSN 1553-7374
1553-7366
IngestDate Sun Oct 01 00:11:20 EDT 2023
Wed Aug 27 01:23:35 EDT 2025
Thu Aug 21 14:14:40 EDT 2025
Thu Jul 10 17:42:11 EDT 2025
Tue Jun 17 21:50:16 EDT 2025
Tue Jun 10 20:32:40 EDT 2025
Fri Jun 27 04:25:19 EDT 2025
Fri Jun 27 05:02:33 EDT 2025
Mon Jul 21 05:42:42 EDT 2025
Thu Apr 24 23:03:29 EDT 2025
Tue Aug 05 12:01:23 EDT 2025
IsDoiOpenAccess true
IsOpenAccess true
IsPeerReviewed true
IsScholarly true
Issue 4
Language English
License This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
Creative Commons Attribution License
LinkModel DirectLink
MergedId FETCHMERGED-LOGICAL-c633t-54ea8078a1b065b4f1de8218ba0a800fdef86f6d5b6f31b45bbe1ab6f55602d3
Notes ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Conceived and designed the experiments: MAJ NS YL. Performed the experiments: MAJ AY MY MC AH AK AT. Analyzed the data: MAJ NS JDL YL EG JPR JS. Contributed reagents/materials/analysis tools: JDL JPR JS. Wrote the paper: MAJ NS YL.
The authors have declared that no competing interests exist.
OpenAccessLink http://journals.scholarsportal.info/openUrl.xqy?doi=10.1371/journal.ppat.1003319
PMID 23658513
PQID 1350152417
PQPubID 23479
ParticipantIDs plos_journals_1351897425
doaj_primary_oai_doaj_org_article_d25017a4d436445f9653e87fc9a16d22
pubmedcentral_primary_oai_pubmedcentral_nih_gov_3635970
proquest_miscellaneous_1350152417
gale_infotracmisc_A330498946
gale_infotracacademiconefile_A330498946
gale_incontextgauss_ISR_A330498946
gale_incontextgauss_ISN_A330498946
pubmed_primary_23658513
crossref_citationtrail_10_1371_journal_ppat_1003319
crossref_primary_10_1371_journal_ppat_1003319
PublicationCentury 2000
PublicationDate 2013-04-01
PublicationDateYYYYMMDD 2013-04-01
PublicationDate_xml – month: 04
  year: 2013
  text: 2013-04-01
  day: 01
PublicationDecade 2010
PublicationPlace United States
PublicationPlace_xml – name: United States
– name: San Francisco, USA
PublicationTitle PLoS pathogens
PublicationTitleAlternate PLoS Pathog
PublicationYear 2013
Publisher Public Library of Science
Public Library of Science (PLoS)
Publisher_xml – name: Public Library of Science
– name: Public Library of Science (PLoS)
References M Klein (ref38) 2011; 188
JM Shaw (ref15) 2011; 85
ED Pulte (ref24) 2007; 121
RJ Rickles (ref47) 2010; 116
S Deaglio (ref8) 2007; 204
B Zhang (ref43) 2010; 70
DB Leal (ref58) 2005; 1746
PW Hunt (ref18) 2011; 6
Y Chern (ref48) 1995; 48
N Seddiki (ref5) 2006; 203
PL Vieira (ref7) 2004; 172
J Schulze Zur Wiesch (ref35) 2011; 85
MV Sitkovsky (ref27) 2004; 22
EM Aandahl (ref52) 1998; 12
AA Erdmann (ref45) 2005; 105
S Rahmouni (ref51) 2001; 15
P Nigam (ref59) 2010; 184
Y Sun (ref61) 2000; 165
E Bjorgo (ref55) 2010; 129
Y Belkaid (ref16) 2005; 6
X Bi (ref12) 2009; 39
T Bopp (ref57) 2007; 204
F Kukulski (ref63) 2005; 1
AL Kinter (ref14) 2004; 200
T Rauen (ref53) 2011; 286
B Fazekas de St Groth (ref17) 2008; 22
CM Hedrich (ref54) 2011; 286
A Ohta (ref28) 2009; 183
M Nikolova (ref30) 2011; 7
L Weiss (ref10) 2004; 104
SA Younes (ref34) 2003; 198
ME Moreno-Fernandez (ref29) 2011; 117
EM Aandahl (ref13) 2004; 78
SH Visovatti (ref31) 2012; 7
E Kaczmarek (ref20) 1996; 271
HL Weiner (ref6) 2001; 182
KM Dwyer (ref23) 2007; 3
S Huang (ref46) 1997; 90
A Ohta (ref26) 2001; 414
J Navarro (ref60) 1998; 72
M Fausther (ref25) 2012; 302
JA Bluestone (ref9) 2011; 365
A Murayama (ref32) 2006; 25
F Porichis (ref33) 2011; 6
LE Averill (ref50) 1988; 115
G Borsellino (ref22) 2007; 110
ME Moreno-Fernandez (ref56) 2012; 28
S Sakaguchi (ref19) 2010; 10
HK Eltzschig (ref62) 2003; 198
LF Thomson (ref40) 1990; 35
MS Alam (ref42) 2009; 199
D Jin (ref44) 2010; 70
A O'Garra (ref3) 2004; 10
GM Kammer (ref49) 1988; 9
W Liu (ref4) 2006; 203
Z Fehervari (ref2) 2004; 16
M Mandapathil (ref36) 2009; 15
L Airas (ref37) 1997; 136
F Kukulski (ref21) 2011; 61
B Liang (ref39) 2008; 180
G Yegutkin (ref41) 2000; 129
DA Vignali (ref1) 2008; 8
H Kared (ref11) 2008; 22
9269779 - Blood. 1997 Aug 15;90(4):1600-10
20053943 - J Immunol. 2010 Feb 15;184(4):1690-701
14676302 - J Exp Med. 2003 Dec 15;198(12):1909-22
12939345 - J Exp Med. 2003 Sep 1;198(5):783-96
14963140 - J Virol. 2004 Mar;78(5):2454-9
19281303 - J Infect Dis. 2009 Feb 15;199(4):494-504
15128781 - J Immunol. 2004 May 15;172(10):5986-93
18404431 - Purinergic Signal. 2007 Mar;3(1-2):171-80
22135310 - Am J Physiol Gastrointest Liver Physiol. 2012 Feb 15;302(4):G447-59
22792409 - PLoS One. 2012;7(7):e40829
20559327 - Nat Rev Immunol. 2010 Jul;10(7):490-500
2137649 - Tissue Antigens. 1990 Jan;35(1):9-19
17555802 - Thromb Res. 2007;121(3):309-17
21880771 - J Virol. 2011 Nov;85(21):11422-34
17502663 - J Exp Med. 2007 Jun 11;204(6):1303-10
2855581 - Immunol Today. 1988 Jul-Aug;9(7-8):222-9
8955160 - J Biol Chem. 1996 Dec 20;271(51):33116-22
21436067 - Blood. 2011 May 19;117(20):5372-80
21750674 - PLoS Pathog. 2011 Jul;7(7):e1002110
15286781 - Nat Med. 2004 Aug;10(8):801-5
19825957 - Clin Cancer Res. 2009 Oct 15;15(20):6348-57
15023414 - Curr Opin Immunol. 2004 Apr;16(2):203-8
11387259 - FASEB J. 2001 Jun;15(8):1466-8
10696091 - Br J Pharmacol. 2000 Mar;129(5):921-6
17449799 - Blood. 2007 Aug 15;110(4):1225-32
16344116 - Biochim Biophys Acta. 2005 Dec 15;1746(2):129-34
18566595 - Nat Rev Immunol. 2008 Jul;8(7):523-32
19005268 - AIDS. 2008 Nov 30;22(18):2451-60
11780065 - Nature. 2001 Dec 20-27;414(6866):916-20
11722636 - Immunol Rev. 2001 Aug;182:207-14
21916808 - AIDS Res Hum Retroviruses. 2012 Jan;28(1):49-53
22025620 - J Biol Chem. 2011 Dec 16;286(50):43437-46
9573235 - J Virol. 1998 Jun;72(6):4712-20
21047964 - J Virol. 2011 Feb;85(3):1287-97
18356596 - AIDS. 2008 Mar 30;22(6):671-83
15032592 - Annu Rev Immunol. 2004;22:657-82
22129258 - N Engl J Med. 2011 Dec 1;365(22):2129-31
21586362 - Adv Pharmacol. 2011;61:263-99
2841027 - Cell Immunol. 1988 Aug;115(1):88-99
9657525 - FASEB J. 1998 Jul;12(10):855-62
7623763 - Mol Pharmacol. 1995 Jul;48(1):1-8
22190184 - J Immunol. 2012 Feb 1;188(3):1091-7
16818676 - J Exp Med. 2006 Jul 10;203(7):1693-700
20682793 - Cancer Res. 2010 Aug 15;70(16):6407-11
15280419 - J Exp Med. 2004 Aug 2;200(3):331-43
15785761 - Nat Immunol. 2005 Apr;6(4):353-60
10925252 - J Immunol. 2000 Aug 15;165(4):1755-61
15271794 - Blood. 2004 Nov 15;104(10):3249-56
9015312 - J Cell Biol. 1997 Jan 27;136(2):421-31
18424711 - J Immunol. 2008 May 1;180(9):5916-26
21502921 - Curr Opin HIV AIDS. 2011 May;6(3):174-80
19089812 - Eur J Immunol. 2009 Jan;39(1):301-9
16818678 - J Exp Med. 2006 Jul 10;203(7):1701-11
21976679 - J Biol Chem. 2011 Dec 16;286(50):43429-36
20382846 - Blood. 2010 Jul 29;116(4):593-602
20123110 - Immunol Lett. 2010 Mar 10;129(1):1-6
18404504 - Purinergic Signal. 2005 Jun;1(2):193-204
21305005 - PLoS One. 2011;6(1):e15924
20179192 - Cancer Res. 2010 Mar 15;70(6):2245-55
19843934 - J Immunol. 2009 Nov 1;183(9):5487-93
16498406 - EMBO J. 2006 Mar 8;25(5):1081-92
15746085 - Blood. 2005 Jun 15;105(12):4707-14
17502665 - J Exp Med. 2007 Jun 11;204(6):1257-65
References_xml – volume: 286
  start-page: 43429
  year: 2011
  ident: ref54
  article-title: cAMP-responsive element modulator (CREM)alpha protein signaling mediates epigenetic remodeling of the human interleukin-2 gene: implications in systemic lupus erythematosus
  publication-title: J Biol Chem
  doi: 10.1074/jbc.M111.299339
– volume: 1
  start-page: 193
  year: 2005
  ident: ref63
  article-title: Comparative hydrolysis of P2 receptor agonists by NTPDases 1, 2, 3 and 8
  publication-title: Purinergic Signal
  doi: 10.1007/s11302-005-6217-x
– volume: 200
  start-page: 331
  year: 2004
  ident: ref14
  article-title: CD25(+)CD4(+) regulatory T cells from the peripheral blood of asymptomatic HIV-infected individuals regulate CD4(+) and CD8(+) HIV-specific T cell immune responses in vitro and are associated with favorable clinical markers of disease status
  publication-title: J Exp Med
  doi: 10.1084/jem.20032069
– volume: 85
  start-page: 11422
  year: 2011
  ident: ref15
  article-title: Increased frequency of regulatory T cells accompanies increased immune activation in rectal mucosae of HIV-positive noncontrollers
  publication-title: J Virol
  doi: 10.1128/JVI.05608-11
– volume: 10
  start-page: 801
  year: 2004
  ident: ref3
  article-title: Regulatory T cells and mechanisms of immune system control
  publication-title: Nat Med
  doi: 10.1038/nm0804-801
– volume: 198
  start-page: 1909
  year: 2003
  ident: ref34
  article-title: HIV-1 viremia prevents the establishment of interleukin 2-producing HIV-specific memory CD4+ T cells endowed with proliferative capacity
  publication-title: J Exp Med
  doi: 10.1084/jem.20031598
– volume: 7
  start-page: e1002110
  year: 2011
  ident: ref30
  article-title: CD39/adenosine pathway is involved in AIDS progression
  publication-title: PLoS Pathog
  doi: 10.1371/journal.ppat.1002110
– volume: 302
  start-page: G447
  year: 2012
  ident: ref25
  article-title: Coexpression of ecto-5′-nucleotidase/CD73 with specific NTPDases differentially regulates adenosine formation in the rat liver
  publication-title: Am J Physiol Gastrointest Liver Physiol
  doi: 10.1152/ajpgi.00165.2011
– volume: 204
  start-page: 1257
  year: 2007
  ident: ref8
  article-title: Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression
  publication-title: J Exp Med
  doi: 10.1084/jem.20062512
– volume: 22
  start-page: 2451
  year: 2008
  ident: ref11
  article-title: HIV-specific regulatory T cells are associated with higher CD4 cell counts in primary infection
  publication-title: AIDS
  doi: 10.1097/QAD.0b013e328319edc0
– volume: 204
  start-page: 1303
  year: 2007
  ident: ref57
  article-title: Cyclic adenosine monophosphate is a key component of regulatory T cell-mediated suppression
  publication-title: J Exp Med
  doi: 10.1084/jem.20062129
– volume: 22
  start-page: 657
  year: 2004
  ident: ref27
  article-title: Physiological control of immune response and inflammatory tissue damage by hypoxia-inducible factors and adenosine A2A receptors
  publication-title: Annu Rev Immunol
  doi: 10.1146/annurev.immunol.22.012703.104731
– volume: 70
  start-page: 2245
  year: 2010
  ident: ref44
  article-title: CD73 on tumor cells impairs antitumor T-cell responses: a novel mechanism of tumor-induced immune suppression
  publication-title: Cancer Res
  doi: 10.1158/0008-5472.CAN-09-3109
– volume: 271
  start-page: 33116
  year: 1996
  ident: ref20
  article-title: Identification and characterization of CD39/vascular ATP diphosphohydrolase
  publication-title: J Biol Chem
  doi: 10.1074/jbc.271.51.33116
– volume: 22
  start-page: 671
  year: 2008
  ident: ref17
  article-title: Regulatory T cells in HIV infection: pathogenic or protective participants in the immune response?
  publication-title: AIDS
  doi: 10.1097/QAD.0b013e3282f466da
– volume: 6
  start-page: e15924
  year: 2011
  ident: ref18
  article-title: A low T regulatory cell response may contribute to both viral control and generalized immune activation in HIV controllers
  publication-title: PLoS One
  doi: 10.1371/journal.pone.0015924
– volume: 35
  start-page: 9
  year: 1990
  ident: ref40
  article-title: Production and characterization of monoclonal antibodies to the glycosyl phosphatidylinositol-anchored lymphocyte differentiation antigen ecto-5′-nucleotidase (CD73)
  publication-title: Tissue Antigens
  doi: 10.1111/j.1399-0039.1990.tb01750.x
– volume: 104
  start-page: 3249
  year: 2004
  ident: ref10
  article-title: Human immunodeficiency virus-driven expansion of CD4+CD25+ regulatory T cells, which suppress HIV-specific CD4 T-cell responses in HIV-infected patients
  publication-title: Blood
  doi: 10.1182/blood-2004-01-0365
– volume: 6
  start-page: 353
  year: 2005
  ident: ref16
  article-title: Natural regulatory T cells in infectious disease
  publication-title: Nat Immunol
  doi: 10.1038/ni1181
– volume: 115
  start-page: 88
  year: 1988
  ident: ref50
  article-title: Control of human T-lymphocyte interleukin-2 production by a cAMP-dependent pathway
  publication-title: Cell Immunol
  doi: 10.1016/0008-8749(88)90164-5
– volume: 116
  start-page: 593
  year: 2010
  ident: ref47
  article-title: Adenosine A2A receptor agonists and PDE inhibitors: a synergistic multitarget mechanism discovered through systematic combination screening in B-cell malignancies
  publication-title: Blood
  doi: 10.1182/blood-2009-11-252668
– volume: 180
  start-page: 5916
  year: 2008
  ident: ref39
  article-title: Regulatory T cells inhibit dendritic cells by lymphocyte activation gene-3 engagement of MHC class II
  publication-title: J Immunol
  doi: 10.4049/jimmunol.180.9.5916
– volume: 203
  start-page: 1693
  year: 2006
  ident: ref5
  article-title: Expression of interleukin (IL)-2 and IL-7 receptors discriminates between human regulatory and activated T cells
  publication-title: J Exp Med
  doi: 10.1084/jem.20060468
– volume: 105
  start-page: 4707
  year: 2005
  ident: ref45
  article-title: Activation of Th1 and Tc1 cell adenosine A2A receptors directly inhibits IL-2 secretion in vitro and IL-2-driven expansion in vivo
  publication-title: Blood
  doi: 10.1182/blood-2004-04-1407
– volume: 61
  start-page: 263
  year: 2011
  ident: ref21
  article-title: Impact of ectoenzymes on p2 and p1 receptor signaling
  publication-title: Adv Pharmacol
  doi: 10.1016/B978-0-12-385526-8.00009-6
– volume: 28
  start-page: 49
  year: 2012
  ident: ref56
  article-title: cAMP During HIV Infection: Friend or Foe?
  publication-title: AIDS Res Hum Retroviruses
  doi: 10.1089/aid.2011.0265
– volume: 117
  start-page: 5372
  year: 2011
  ident: ref29
  article-title: Regulatory T cells control HIV replication in activated T cells through a cAMP-dependent mechanism
  publication-title: Blood
  doi: 10.1182/blood-2010-12-323162
– volume: 365
  start-page: 2129
  year: 2011
  ident: ref9
  article-title: The yin and yang of interleukin-2-mediated immunotherapy
  publication-title: N Engl J Med
  doi: 10.1056/NEJMe1110900
– volume: 9
  start-page: 222
  year: 1988
  ident: ref49
  article-title: The adenylate cyclase-cAMP-protein kinase A pathway and regulation of the immune response
  publication-title: Immunol Today
  doi: 10.1016/0167-5699(88)91220-0
– volume: 199
  start-page: 494
  year: 2009
  ident: ref42
  article-title: CD73 is expressed by human regulatory T helper cells and suppresses proinflammatory cytokine production and Helicobacter felis-induced gastritis in mice
  publication-title: J Infect Dis
  doi: 10.1086/596205
– volume: 85
  start-page: 1287
  year: 2011
  ident: ref35
  article-title: Comprehensive analysis of frequency and phenotype of T regulatory cells in HIV infection: CD39 expression of FoxP3+ T regulatory cells correlates with progressive disease
  publication-title: J Virol
  doi: 10.1128/JVI.01758-10
– volume: 8
  start-page: 523
  year: 2008
  ident: ref1
  article-title: How regulatory T cells work
  publication-title: Nat Rev Immunol
  doi: 10.1038/nri2343
– volume: 12
  start-page: 855
  year: 1998
  ident: ref52
  article-title: Protein kinase A type I antagonist restores immune responses of T cells from HIV-infected patients
  publication-title: FASEB J
  doi: 10.1096/fasebj.12.10.855
– volume: 129
  start-page: 921
  year: 2000
  ident: ref41
  article-title: Effect of shear stress on the release of soluble ecto-enzymes ATPase and 5′-nucleotidase along with endogenous ATP from vascular endothelial cells
  publication-title: Br J Pharmacol
  doi: 10.1038/sj.bjp.0703136
– volume: 90
  start-page: 1600
  year: 1997
  ident: ref46
  article-title: Role of A2a extracellular adenosine receptor-mediated signaling in adenosine-mediated inhibition of T-cell activation and expansion
  publication-title: Blood
  doi: 10.1182/blood.V90.4.1600
– volume: 183
  start-page: 5487
  year: 2009
  ident: ref28
  article-title: A2A adenosine receptor may allow expansion of T cells lacking effector functions in extracellular adenosine-rich microenvironments
  publication-title: J Immunol
  doi: 10.4049/jimmunol.0901247
– volume: 16
  start-page: 203
  year: 2004
  ident: ref2
  article-title: Development and function of CD25+CD4+ regulatory T cells
  publication-title: Curr Opin Immunol
  doi: 10.1016/j.coi.2004.01.004
– volume: 203
  start-page: 1701
  year: 2006
  ident: ref4
  article-title: CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells
  publication-title: J Exp Med
  doi: 10.1084/jem.20060772
– volume: 414
  start-page: 916
  year: 2001
  ident: ref26
  article-title: Role of G-protein-coupled adenosine receptors in downregulation of inflammation and protection from tissue damage
  publication-title: Nature
  doi: 10.1038/414916a
– volume: 48
  start-page: 1
  year: 1995
  ident: ref48
  article-title: Regulation of adenylyl cyclase type VI activity during desensitization of the A2a adenosine receptor-mediated cyclic AMP response: role for protein phosphatase 2A
  publication-title: Mol Pharmacol
  doi: 10.1016/S0026-895X(25)10033-3
– volume: 286
  start-page: 43437
  year: 2011
  ident: ref53
  article-title: cAMP-responsive element modulator (CREM)alpha protein induces interleukin 17A expression and mediates epigenetic alterations at the interleukin-17A gene locus in patients with systemic lupus erythematosus
  publication-title: J Biol Chem
  doi: 10.1074/jbc.M111.299313
– volume: 121
  start-page: 309
  year: 2007
  ident: ref24
  article-title: CD39/NTPDase-1 activity and expression in normal leukocytes
  publication-title: Thromb Res
  doi: 10.1016/j.thromres.2007.04.008
– volume: 165
  start-page: 1755
  year: 2000
  ident: ref61
  article-title: Infection of CD4+ memory T cells by HIV-1 requires expression of phosphodiesterase 4
  publication-title: J Immunol
  doi: 10.4049/jimmunol.165.4.1755
– volume: 172
  start-page: 5986
  year: 2004
  ident: ref7
  article-title: IL-10-secreting regulatory T cells do not express Foxp3 but have comparable regulatory function to naturally occurring CD4+CD25+ regulatory T cells
  publication-title: J Immunol
  doi: 10.4049/jimmunol.172.10.5986
– volume: 1746
  start-page: 129
  year: 2005
  ident: ref58
  article-title: HIV infection is associated with increased NTPDase activity that correlates with CD39-positive lymphocytes
  publication-title: Biochim Biophys Acta
  doi: 10.1016/j.bbamcr.2005.10.009
– volume: 72
  start-page: 4712
  year: 1998
  ident: ref60
  article-title: Inhibition of phosphodiesterase type IV suppresses human immunodeficiency virus type 1 replication and cytokine production in primary T cells: involvement of NF-kappaB and NFAT
  publication-title: J Virol
  doi: 10.1128/JVI.72.6.4712-4720.1998
– volume: 188
  start-page: 1091
  year: 2011
  ident: ref38
  article-title: Repression of cyclic adenosine monophosphate upregulation disarms and expands human regulatory T cells
  publication-title: J Immunol
  doi: 10.4049/jimmunol.1102045
– volume: 198
  start-page: 783
  year: 2003
  ident: ref62
  article-title: Coordinated adenine nucleotide phosphohydrolysis and nucleoside signaling in posthypoxic endothelium: role of ectonucleotidases and adenosine A2B receptors
  publication-title: J Exp Med
  doi: 10.1084/jem.20030891
– volume: 182
  start-page: 207
  year: 2001
  ident: ref6
  article-title: Induction and mechanism of action of transforming growth factor-beta-secreting Th3 regulatory cells
  publication-title: Immunol Rev
  doi: 10.1034/j.1600-065X.2001.1820117.x
– volume: 78
  start-page: 2454
  year: 2004
  ident: ref13
  article-title: Human CD4+ CD25+ regulatory T cells control T-cell responses to human immunodeficiency virus and cytomegalovirus antigens
  publication-title: J Virol
  doi: 10.1128/JVI.78.5.2454-2459.2004
– volume: 7
  start-page: e40829
  year: 2012
  ident: ref31
  article-title: Increased CD39 nucleotidase activity on microparticles from patients with idiopathic pulmonary arterial hypertension
  publication-title: PLoS One
  doi: 10.1371/journal.pone.0040829
– volume: 6
  start-page: 174
  year: 2011
  ident: ref33
  article-title: HIV-specific CD4 T cells and immune control of viral replication
  publication-title: Curr Opin HIV AIDS
  doi: 10.1097/COH.0b013e3283454058
– volume: 25
  start-page: 1081
  year: 2006
  ident: ref32
  article-title: A specific CpG site demethylation in the human interleukin 2 gene promoter is an epigenetic memory
  publication-title: Embo J
  doi: 10.1038/sj.emboj.7601012
– volume: 110
  start-page: 1225
  year: 2007
  ident: ref22
  article-title: Expression of ectonucleotidase CD39 by Foxp3+ Treg cells: hydrolysis of extracellular ATP and immune suppression
  publication-title: Blood
  doi: 10.1182/blood-2006-12-064527
– volume: 39
  start-page: 301
  year: 2009
  ident: ref12
  article-title: High frequency and proliferation of CD4+ FOXP3+ Treg in HIV-1-infected patients with low CD4 counts
  publication-title: Eur J Immunol
  doi: 10.1002/eji.200838667
– volume: 129
  start-page: 1
  year: 2010
  ident: ref55
  article-title: Novel mechanism of signaling by CD28
  publication-title: Immunol Lett
  doi: 10.1016/j.imlet.2010.01.007
– volume: 70
  start-page: 6407
  year: 2010
  ident: ref43
  article-title: CD73: a novel target for cancer immunotherapy
  publication-title: Cancer Res
  doi: 10.1158/0008-5472.CAN-10-1544
– volume: 15
  start-page: 6348
  year: 2009
  ident: ref36
  article-title: Increased ectonucleotidase expression and activity in regulatory T cells of patients with head and neck cancer
  publication-title: Clin Cancer Res
  doi: 10.1158/1078-0432.CCR-09-1143
– volume: 136
  start-page: 421
  year: 1997
  ident: ref37
  article-title: Differential regulation and function of CD73, a glycosyl-phosphatidylinositol-linked 70-kD adhesion molecule, on lymphocytes and endothelial cells
  publication-title: J Cell Biol
  doi: 10.1083/jcb.136.2.421
– volume: 184
  start-page: 1690
  year: 2010
  ident: ref59
  article-title: Expansion of FOXP3+ CD8 T cells with suppressive potential in colorectal mucosa following a pathogenic simian immunodeficiency virus infection correlates with diminished antiviral T cell response and viral control
  publication-title: J Immunol
  doi: 10.4049/jimmunol.0902955
– volume: 15
  start-page: 1466
  year: 2001
  ident: ref51
  article-title: Increased cAMP levels and protein kinase (PKA) type I activation in CD4+ T cells and B cells contribute to retrovirus-induced immunodeficiency of mice (MAIDS): a useful in vivo model for drug testing
  publication-title: FASEB J
  doi: 10.1096/fj.00-0813fje
– volume: 10
  start-page: 490
  year: 2010
  ident: ref19
  article-title: FOXP3+ regulatory T cells in the human immune system
  publication-title: Nat Rev Immunol
  doi: 10.1038/nri2785
– volume: 3
  start-page: 171
  year: 2007
  ident: ref23
  article-title: CD39 and control of cellular immune responses
  publication-title: Purinergic Signal
  doi: 10.1007/s11302-006-9050-y
– reference: 17555802 - Thromb Res. 2007;121(3):309-17
– reference: 9657525 - FASEB J. 1998 Jul;12(10):855-62
– reference: 22025620 - J Biol Chem. 2011 Dec 16;286(50):43437-46
– reference: 18404431 - Purinergic Signal. 2007 Mar;3(1-2):171-80
– reference: 15785761 - Nat Immunol. 2005 Apr;6(4):353-60
– reference: 20053943 - J Immunol. 2010 Feb 15;184(4):1690-701
– reference: 19089812 - Eur J Immunol. 2009 Jan;39(1):301-9
– reference: 21880771 - J Virol. 2011 Nov;85(21):11422-34
– reference: 21502921 - Curr Opin HIV AIDS. 2011 May;6(3):174-80
– reference: 22129258 - N Engl J Med. 2011 Dec 1;365(22):2129-31
– reference: 21916808 - AIDS Res Hum Retroviruses. 2012 Jan;28(1):49-53
– reference: 15032592 - Annu Rev Immunol. 2004;22:657-82
– reference: 19281303 - J Infect Dis. 2009 Feb 15;199(4):494-504
– reference: 2855581 - Immunol Today. 1988 Jul-Aug;9(7-8):222-9
– reference: 20559327 - Nat Rev Immunol. 2010 Jul;10(7):490-500
– reference: 15128781 - J Immunol. 2004 May 15;172(10):5986-93
– reference: 21047964 - J Virol. 2011 Feb;85(3):1287-97
– reference: 18356596 - AIDS. 2008 Mar 30;22(6):671-83
– reference: 9573235 - J Virol. 1998 Jun;72(6):4712-20
– reference: 22792409 - PLoS One. 2012;7(7):e40829
– reference: 16344116 - Biochim Biophys Acta. 2005 Dec 15;1746(2):129-34
– reference: 21750674 - PLoS Pathog. 2011 Jul;7(7):e1002110
– reference: 21436067 - Blood. 2011 May 19;117(20):5372-80
– reference: 19843934 - J Immunol. 2009 Nov 1;183(9):5487-93
– reference: 16818676 - J Exp Med. 2006 Jul 10;203(7):1693-700
– reference: 20179192 - Cancer Res. 2010 Mar 15;70(6):2245-55
– reference: 2841027 - Cell Immunol. 1988 Aug;115(1):88-99
– reference: 21976679 - J Biol Chem. 2011 Dec 16;286(50):43429-36
– reference: 17449799 - Blood. 2007 Aug 15;110(4):1225-32
– reference: 15271794 - Blood. 2004 Nov 15;104(10):3249-56
– reference: 9015312 - J Cell Biol. 1997 Jan 27;136(2):421-31
– reference: 20123110 - Immunol Lett. 2010 Mar 10;129(1):1-6
– reference: 18424711 - J Immunol. 2008 May 1;180(9):5916-26
– reference: 17502663 - J Exp Med. 2007 Jun 11;204(6):1303-10
– reference: 14963140 - J Virol. 2004 Mar;78(5):2454-9
– reference: 8955160 - J Biol Chem. 1996 Dec 20;271(51):33116-22
– reference: 16818678 - J Exp Med. 2006 Jul 10;203(7):1701-11
– reference: 2137649 - Tissue Antigens. 1990 Jan;35(1):9-19
– reference: 19005268 - AIDS. 2008 Nov 30;22(18):2451-60
– reference: 19825957 - Clin Cancer Res. 2009 Oct 15;15(20):6348-57
– reference: 12939345 - J Exp Med. 2003 Sep 1;198(5):783-96
– reference: 21305005 - PLoS One. 2011;6(1):e15924
– reference: 21586362 - Adv Pharmacol. 2011;61:263-99
– reference: 18404504 - Purinergic Signal. 2005 Jun;1(2):193-204
– reference: 10696091 - Br J Pharmacol. 2000 Mar;129(5):921-6
– reference: 11722636 - Immunol Rev. 2001 Aug;182:207-14
– reference: 11387259 - FASEB J. 2001 Jun;15(8):1466-8
– reference: 15023414 - Curr Opin Immunol. 2004 Apr;16(2):203-8
– reference: 11780065 - Nature. 2001 Dec 20-27;414(6866):916-20
– reference: 15746085 - Blood. 2005 Jun 15;105(12):4707-14
– reference: 20382846 - Blood. 2010 Jul 29;116(4):593-602
– reference: 7623763 - Mol Pharmacol. 1995 Jul;48(1):1-8
– reference: 18566595 - Nat Rev Immunol. 2008 Jul;8(7):523-32
– reference: 9269779 - Blood. 1997 Aug 15;90(4):1600-10
– reference: 17502665 - J Exp Med. 2007 Jun 11;204(6):1257-65
– reference: 22190184 - J Immunol. 2012 Feb 1;188(3):1091-7
– reference: 22135310 - Am J Physiol Gastrointest Liver Physiol. 2012 Feb 15;302(4):G447-59
– reference: 15280419 - J Exp Med. 2004 Aug 2;200(3):331-43
– reference: 20682793 - Cancer Res. 2010 Aug 15;70(16):6407-11
– reference: 10925252 - J Immunol. 2000 Aug 15;165(4):1755-61
– reference: 15286781 - Nat Med. 2004 Aug;10(8):801-5
– reference: 14676302 - J Exp Med. 2003 Dec 15;198(12):1909-22
– reference: 16498406 - EMBO J. 2006 Mar 8;25(5):1081-92
SSID ssj0041316
Score 2.3560095
Snippet The mechanisms by which Regulatory T cells suppress IL-2 production of effector CD4+ T cells in pathological conditions are unclear. A subpopulation of human...
  The mechanisms by which Regulatory T cells suppress IL-2 production of effector CD4+ T cells in pathological conditions are unclear. A subpopulation of human...
SourceID plos
doaj
pubmedcentral
proquest
gale
pubmed
crossref
SourceType Open Website
Open Access Repository
Aggregation Database
Index Database
Enrichment Source
StartPage e1003319
SubjectTerms 5'-Nucleotidase - metabolism
Adenosine
Adenosine - metabolism
Antibodies, Monoclonal - immunology
Antigens, CD - biosynthesis
Antigens, CD - immunology
Antigens, CD - metabolism
Apyrase - biosynthesis
Apyrase - immunology
Apyrase - metabolism
Biology
Cell Proliferation
Cyclic AMP - metabolism
DNA Methylation
Health aspects
HIV
HIV infection
HIV Infections - immunology
HIV-1 - immunology
Host-parasite relationships
Human immunodeficiency virus
Humans
Immune system
Interleukin-2
Interleukin-2 - biosynthesis
Interleukin-2 - genetics
Lymphocyte Activation
Medical research
Medicine
Physiological aspects
Promoter Regions, Genetic
Proteins
Receptor, Adenosine A2A - metabolism
T cell receptors
T cells
T-Lymphocyte Subsets - immunology
T-Lymphocyte Subsets - metabolism
T-Lymphocytes, Regulatory - immunology
T-Lymphocytes, Regulatory - metabolism
SummonAdditionalLinks – databaseName: Directory of Open Access Journals (DOAJ)
  dbid: DOA
  link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV1Nb9QwELXQSkhcEN8NFGQQEqewiZ04ybEUql0EPZQF9WbZcdxWWiXRZlew_54ZO4k2CNQLxyTjg2fGM-N4_B4hbxmLyqgoWWhgJcEGJbehjosSCjk8M7KwGRN4wfnruVh8Tz5fppcHVF_YE-bhgb3i5gZydJypxCQcUndqC5HyKs9sWahYGOaiL-S8YTPlYzBEZkd6iqQ4YcaF6C_N8Sye9zZ637YK4aMjzhFl5yApOez-MULP2nXT_a38_LOL8iAtnT0g9_t6kp74eTwkd6r6EbnrGSb3j8mvC88132z2dEXxL31H6-rKoX2v91S5bg66_BIy2nrsV7ATbSz1fR7NZhzVE_rQ04-8mCuDGONQoFJkNP6p9vSmpovlDzr0dtVPyOrs0-p0EfZkC2EpON-GaVIpxJ5XsYaqRCc2NlUO-V-rCN5H1lQ2F1aYVAvLY52kWlexgocUaiZm-FMyq5u6OiI01xkEDVvqJDcJBIScQ9hVtkhzY1mmWUD4oGxZ9kDkyIexlu50LYMNidedRBPJ3kQBCcdRrQfiuEX-A9pxlEUYbfcCnEv2ziVvc66AvEEvkAiUUWMnzpXadZ1cfjuXJ_gjCNHrxT-FLiZC73oh28BkS9XffgCVIQDXRPJ4IgnLvZx8PkKPHObcSaRYzGFXyNKAvB68VOIobJ-rq2bnZKDsg2ItC8gz77WjYhgXeDTMA5JN_HmiuemX-ubaAZFzqFaLLHr-P1T9gtxjjmkEm6KOyWy72VUvod7b6lduaf8GLAlP_A
  priority: 102
  providerName: Directory of Open Access Journals
Title Regulatory T Cells Negatively Affect IL-2 Production of Effector T Cells through CD39/Adenosine Pathway in HIV Infection
URI https://www.ncbi.nlm.nih.gov/pubmed/23658513
https://www.proquest.com/docview/1350152417
https://pubmed.ncbi.nlm.nih.gov/PMC3635970
https://doaj.org/article/d25017a4d436445f9653e87fc9a16d22
http://dx.doi.org/10.1371/journal.ppat.1003319
Volume 9
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
link http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwhV3db9MwELdGJyReEN8rjMogJJ4ykjixkweEtrGpRaxCpUN9i-w4LpOqpDStWP577pwPEbSKxyTnKDnfnX-2z78j5J3vu6kbp76jwZNgghIZR3lxCkAO94wMTMY4HnC-mvLxdfBlES4OSFuztVFgeefUDutJXW9WJ7e_qk_g8B9t1QbhtY1O1muJhNAuY8gDeghjk0BXvQq6fQWI2B5vDtDta4n0wIzjbhnrjVWW0r8L3IP1qijvQqX_Jlf-NVpdPiIPG5hJT2u7eEwOsvwJuV8XnqyekttZXYK-2FR0TnHxvqR5trQk4KuKSpvkQSdfHZ-ua0pY6D5aGFqnfxSbrlVT54eef2bxB6mRehxwK8VCx79lRW9yOp78oG3KV_6MzC8v5udjp6nB4KScsa0TBplESnrpKQArKjCeziKABUq6cN81OjMRN1yHihvmqSBUKvMkXIQApXzNnpNBXuTZEaGREhBLTKqCSAcQJyIG0ViaOIy08YXyh4S1yk7Shp8cy2SsErvpJmCeUusuwd5Kmt4aEqdrta75Of4jf4b92Mkiu7a9UWyWSeOsiQZc6AkZ6IABXAxNzEOWRcKksfS49uFT36IVJMifkWOCzlLuyjKZfJ8mp7g-hKT2fK_QrCf0vhEyBfxsKptDEaAy5OXqSR73JCEKpL3HR2iR7T-XCVZejGCy6IdD8qa10gRbYVZdnhU7KwNoEP1kSF7UVtsppvWBIRE9e-5prv8kv_lp-ckZgNhYuC_3vvMVeeDbqiKYAHVMBtvNLnsN2G6rRuSeWIgROTy7mH6bjewKyci68B_6zk-v
linkProvider Scholars Portal
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Regulatory+T+cells+negatively+affect+IL-2+production+of+effector+T+cells+through+CD39%2Fadenosine+pathway+in+HIV+infection&rft.jtitle=PLoS+pathogens&rft.au=Jenabian%2C+Mohammad-Ali&rft.au=Seddiki%2C+Nabila&rft.au=Yatim%2C+Ahmad&rft.au=Carriere%2C+Matthieu&rft.date=2013-04-01&rft.eissn=1553-7374&rft.volume=9&rft.issue=4&rft.spage=e1003319&rft_id=info:doi/10.1371%2Fjournal.ppat.1003319&rft_id=info%3Apmid%2F23658513&rft.externalDocID=23658513
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1553-7374&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1553-7374&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1553-7374&client=summon