CD39/adenosine pathway is involved in AIDS progression
HIV-1 infection is characterized by a chronic activation of the immune system and suppressed function of T lymphocytes. Regulatory CD4+ CD25(high) FoxP3+CD127(low) T cells (Treg) play a key role in both conditions. Here, we show that HIV-1 positive patients have a significant increase of Treg-associ...
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| Veröffentlicht in: | PLoS pathogens 2011-07, Vol.7 (7), p.e1002110-e1002110 |
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| creator | Nikolova, Maria Carriere, Matthieu Jenabian, Mohammad-Ali Limou, Sophie Younas, Mehwish Kök, Ayrin Huë, Sophie Seddiki, Nabila Hulin, Anne Delaneau, Olivier Schuitemaker, Hanneke Herbeck, Joshua T Mullins, James I Muhtarova, Maria Bensussan, Armand Zagury, Jean-François Lelievre, Jean-Daniel Lévy, Yves |
| description | HIV-1 infection is characterized by a chronic activation of the immune system and suppressed function of T lymphocytes. Regulatory CD4+ CD25(high) FoxP3+CD127(low) T cells (Treg) play a key role in both conditions. Here, we show that HIV-1 positive patients have a significant increase of Treg-associated expression of CD39/ENTPD1, an ectoenzyme which in concert with CD73 generates adenosine. We show in vitro that the CD39/adenosine axis is involved in Treg suppression in HIV infection. Treg inhibitory effects are relieved by CD39 down modulation and are reproduced by an adenosine-agonist in accordance with a higher expression of the adenosine A2A receptor on patients' T cells. Notably, the expansion of the Treg CD39+ correlates with the level of immune activation and lower CD4+ counts in HIV-1 infected patients. Finally, in a genetic association study performed in three different cohorts, we identified a CD39 gene polymorphism that was associated with down-modulated CD39 expression and a slower progression to AIDS. |
| doi_str_mv | 10.1371/journal.ppat.1002110 |
| format | Article |
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Regulatory CD4+ CD25(high) FoxP3+CD127(low) T cells (Treg) play a key role in both conditions. Here, we show that HIV-1 positive patients have a significant increase of Treg-associated expression of CD39/ENTPD1, an ectoenzyme which in concert with CD73 generates adenosine. We show in vitro that the CD39/adenosine axis is involved in Treg suppression in HIV infection. Treg inhibitory effects are relieved by CD39 down modulation and are reproduced by an adenosine-agonist in accordance with a higher expression of the adenosine A2A receptor on patients' T cells. Notably, the expansion of the Treg CD39+ correlates with the level of immune activation and lower CD4+ counts in HIV-1 infected patients. Finally, in a genetic association study performed in three different cohorts, we identified a CD39 gene polymorphism that was associated with down-modulated CD39 expression and a slower progression to AIDS.</description><identifier>ISSN: 1553-7374</identifier><identifier>ISSN: 1553-7366</identifier><identifier>EISSN: 1553-7374</identifier><identifier>DOI: 10.1371/journal.ppat.1002110</identifier><identifier>PMID: 21750674</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acquired immune deficiency syndrome ; Adenosine ; Adenosine - immunology ; Adenosine - metabolism ; AIDS ; AIDS (Disease) ; Antigens, CD - immunology ; Antigens, CD - metabolism ; Apyrase - immunology ; Apyrase - metabolism ; Biochemistry, Molecular Biology ; Biomarkers - metabolism ; Bulgaria - epidemiology ; Cell Proliferation ; Cells, Cultured ; Cloning ; Development and progression ; Disease Progression ; Down-Regulation ; Experiments ; Forkhead Transcription Factors - immunology ; Forkhead Transcription Factors - metabolism ; France - epidemiology ; Gene Expression ; Health aspects ; HIV ; HIV Infections - immunology ; HIV Infections - metabolism ; HIV Infections - mortality ; Human immunodeficiency virus ; Humans ; Hypotheses ; Immune system ; Life Sciences ; Lymphocyte Activation ; Lymphocytes ; Medicine ; Physiological aspects ; Polymorphism, Genetic ; Receptor, Adenosine A2A - genetics ; Receptor, Adenosine A2A - metabolism ; Survival Rate ; T cell receptors ; T cells ; T-Lymphocytes, Regulatory - immunology ; T-Lymphocytes, Regulatory - metabolism</subject><ispartof>PLoS pathogens, 2011-07, Vol.7 (7), p.e1002110-e1002110</ispartof><rights>COPYRIGHT 2011 Public Library of Science</rights><rights>2011 Nikolova 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: Nikolova M, Carriere M, Jenabian M-A, Limou S, Younas M, et al. (2011) CD39/Adenosine Pathway Is Involved in AIDS Progression. 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Regulatory CD4+ CD25(high) FoxP3+CD127(low) T cells (Treg) play a key role in both conditions. Here, we show that HIV-1 positive patients have a significant increase of Treg-associated expression of CD39/ENTPD1, an ectoenzyme which in concert with CD73 generates adenosine. We show in vitro that the CD39/adenosine axis is involved in Treg suppression in HIV infection. Treg inhibitory effects are relieved by CD39 down modulation and are reproduced by an adenosine-agonist in accordance with a higher expression of the adenosine A2A receptor on patients' T cells. Notably, the expansion of the Treg CD39+ correlates with the level of immune activation and lower CD4+ counts in HIV-1 infected patients. Finally, in a genetic association study performed in three different cohorts, we identified a CD39 gene polymorphism that was associated with down-modulated CD39 expression and a slower progression to AIDS.</description><subject>Acquired immune deficiency syndrome</subject><subject>Adenosine</subject><subject>Adenosine - immunology</subject><subject>Adenosine - metabolism</subject><subject>AIDS</subject><subject>AIDS (Disease)</subject><subject>Antigens, CD - immunology</subject><subject>Antigens, CD - metabolism</subject><subject>Apyrase - immunology</subject><subject>Apyrase - metabolism</subject><subject>Biochemistry, Molecular Biology</subject><subject>Biomarkers - metabolism</subject><subject>Bulgaria - epidemiology</subject><subject>Cell Proliferation</subject><subject>Cells, Cultured</subject><subject>Cloning</subject><subject>Development and progression</subject><subject>Disease Progression</subject><subject>Down-Regulation</subject><subject>Experiments</subject><subject>Forkhead Transcription Factors - immunology</subject><subject>Forkhead Transcription Factors - metabolism</subject><subject>France - epidemiology</subject><subject>Gene Expression</subject><subject>Health aspects</subject><subject>HIV</subject><subject>HIV Infections - immunology</subject><subject>HIV Infections - metabolism</subject><subject>HIV Infections - mortality</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Hypotheses</subject><subject>Immune system</subject><subject>Life Sciences</subject><subject>Lymphocyte Activation</subject><subject>Lymphocytes</subject><subject>Medicine</subject><subject>Physiological aspects</subject><subject>Polymorphism, Genetic</subject><subject>Receptor, Adenosine A2A - genetics</subject><subject>Receptor, Adenosine A2A - metabolism</subject><subject>Survival Rate</subject><subject>T cell 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pathway is involved in AIDS progression</title><author>Nikolova, Maria ; Carriere, Matthieu ; Jenabian, Mohammad-Ali ; Limou, Sophie ; Younas, Mehwish ; Kök, Ayrin ; Huë, Sophie ; Seddiki, Nabila ; Hulin, Anne ; Delaneau, Olivier ; Schuitemaker, Hanneke ; Herbeck, Joshua T ; Mullins, James I ; Muhtarova, Maria ; Bensussan, Armand ; Zagury, Jean-François ; Lelievre, Jean-Daniel ; Lévy, Yves</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c641t-74445c3e7bf31a1dc5be2210e096662d68ca837b2ed9a850ca50fa378f98178f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Acquired immune deficiency syndrome</topic><topic>Adenosine</topic><topic>Adenosine - immunology</topic><topic>Adenosine - metabolism</topic><topic>AIDS</topic><topic>AIDS (Disease)</topic><topic>Antigens, CD - immunology</topic><topic>Antigens, CD - metabolism</topic><topic>Apyrase - immunology</topic><topic>Apyrase - 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| recordid | cdi_plos_journals_1289068207 |
| source | MEDLINE; NCBI_PubMed Central（免费）; DOAJ Directory of Open Access Journals; PLoS_OA刊; EZB*; PubMed Central Open Access |
| subjects | Acquired immune deficiency syndrome Adenosine Adenosine - immunology Adenosine - metabolism AIDS AIDS (Disease) Antigens, CD - immunology Antigens, CD - metabolism Apyrase - immunology Apyrase - metabolism Biochemistry, Molecular Biology Biomarkers - metabolism Bulgaria - epidemiology Cell Proliferation Cells, Cultured Cloning Development and progression Disease Progression Down-Regulation Experiments Forkhead Transcription Factors - immunology Forkhead Transcription Factors - metabolism France - epidemiology Gene Expression Health aspects HIV HIV Infections - immunology HIV Infections - metabolism HIV Infections - mortality Human immunodeficiency virus Humans Hypotheses Immune system Life Sciences Lymphocyte Activation Lymphocytes Medicine Physiological aspects Polymorphism, Genetic Receptor, Adenosine A2A - genetics Receptor, Adenosine A2A - metabolism Survival Rate T cell receptors T cells T-Lymphocytes, Regulatory - immunology T-Lymphocytes, Regulatory - metabolism |
| title | CD39/adenosine pathway is involved in AIDS progression |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-18T14%3A49%3A55IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=CD39/adenosine%20pathway%20is%20involved%20in%20AIDS%20progression&rft.jtitle=PLoS%20pathogens&rft.au=Nikolova,%20Maria&rft.date=2011-07-01&rft.volume=7&rft.issue=7&rft.spage=e1002110&rft.epage=e1002110&rft.pages=e1002110-e1002110&rft.issn=1553-7374&rft.eissn=1553-7374&rft_id=info:doi/10.1371/journal.ppat.1002110&rft_dat=%3Cgale_plos_%3EA263659769%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1289068207&rft_id=info:pmid/21750674&rft_galeid=A263659769&rft_doaj_id=oai_doaj_org_article_6978a6a1af86471db9fda97b11c647d1&rfr_iscdi=true |