HAART reduces death ligand but not death receptors in lymphoid tissue of HIV-infected patients and simian immunodeficiency virus-infected macaques
To determine how antiretroviral therapy (ART) or HAART affects the expression of apoptotic ligands and their death receptors in the blood and lymphoid tissues of HIV-infected patients and simian immunodeficiency virus-infected macaques. We analyzed the mRNA expression of death molecules [tumor necro...
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| Veröffentlicht in: | AIDS (London) 2009-01, Vol.23 (1), p.35-40 |
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| creator | HERBEUVAL, Jean-Philippe NILSSON, Jakob BOASSO, Adriano HARDY, Andrew W VACCARI, Monica CECCHINATO, Valentina VALERI, Valerio FRANCHINI, Genoveffa ANDERSSON, Jan SHEARER, Gene M |
| description | To determine how antiretroviral therapy (ART) or HAART affects the expression of apoptotic ligands and their death receptors in the blood and lymphoid tissues of HIV-infected patients and simian immunodeficiency virus-infected macaques.
We analyzed the mRNA expression of death molecules [tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and FasL] and their receptors (DR5 and Fas) in blood and tonsils from HIV-infected patients (HIV positive), HIV-infected patients receiving HAART and HIV-uninfected (HIV negative) donors in a cross-sectional study. We comparatively analyzed mRNA expression of TRAIL and DR5 in blood and lymph nodes collected longitudinally from simian immunodeficiency virus-infected macaques before and after ART.
Expression of TRAIL, FasL, DR5 and Fas was elevated in circulating CD4 T cells from a group of HIV-positive patients as compared with that from both HIV-negative donors and HAART patients. In a different study group, TRAIL, FasL, DR5 and Fas were increased in tonsils of HIV-positive patients as compared with HIV-negative donors and HAART patients. However, tonsils from HAART patients showed reduced expression of TRAIL and FasL but not DR5 and Fas as compared with HIV-positive patients. Similarly, data obtained in a longitudinal study of simian immunodeficiency virus-infected macaques showed that ART reduced both TRAIL and DR5 in peripheral blood but only TRAIL and not DR5 in lymph nodes from the same animals.
These findings suggest that HAART or ART is ineffective in reducing the expression of apoptotic death receptors in lymphoid tissue. However, analysis limited to blood leukocytes may not reveal such a defect. Our results highlight the persistence of an underlying immunologic condition that may prevent therapy-induced restoration of CD4 T cells in lymphoid tissue. |
| doi_str_mv | 10.1097/QAD.0b013e32831cb907 |
| format | Article |
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We analyzed the mRNA expression of death molecules [tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and FasL] and their receptors (DR5 and Fas) in blood and tonsils from HIV-infected patients (HIV positive), HIV-infected patients receiving HAART and HIV-uninfected (HIV negative) donors in a cross-sectional study. We comparatively analyzed mRNA expression of TRAIL and DR5 in blood and lymph nodes collected longitudinally from simian immunodeficiency virus-infected macaques before and after ART.
Expression of TRAIL, FasL, DR5 and Fas was elevated in circulating CD4 T cells from a group of HIV-positive patients as compared with that from both HIV-negative donors and HAART patients. In a different study group, TRAIL, FasL, DR5 and Fas were increased in tonsils of HIV-positive patients as compared with HIV-negative donors and HAART patients. However, tonsils from HAART patients showed reduced expression of TRAIL and FasL but not DR5 and Fas as compared with HIV-positive patients. Similarly, data obtained in a longitudinal study of simian immunodeficiency virus-infected macaques showed that ART reduced both TRAIL and DR5 in peripheral blood but only TRAIL and not DR5 in lymph nodes from the same animals.
These findings suggest that HAART or ART is ineffective in reducing the expression of apoptotic death receptors in lymphoid tissue. However, analysis limited to blood leukocytes may not reveal such a defect. Our results highlight the persistence of an underlying immunologic condition that may prevent therapy-induced restoration of CD4 T cells in lymphoid tissue.</description><identifier>ISSN: 0269-9370</identifier><identifier>ISSN: 1473-5571</identifier><identifier>EISSN: 1473-5571</identifier><identifier>DOI: 10.1097/QAD.0b013e32831cb907</identifier><identifier>PMID: 19050384</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Animals ; Anti-HIV Agents ; Anti-HIV Agents - pharmacology ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; Antiretroviral Therapy, Highly Active ; Antiviral agents ; Biological and medical sciences ; Cross-Sectional Studies ; Fas Ligand Protein ; Fas Ligand Protein - genetics ; Fas Ligand Protein - metabolism ; Gene Expression Regulation ; Gene Expression Regulation - drug effects ; HIV Infections ; HIV Infections - drug therapy ; HIV Infections - immunology ; Human immunodeficiency virus ; Human viral diseases ; Humans ; Immunodeficiencies ; Immunodeficiencies. Immunoglobulinopathies ; Immunopathology ; Infectious diseases ; Life Sciences ; Lymph Nodes ; Lymph Nodes - immunology ; Lymphoid Tissue ; Lymphoid Tissue - immunology ; Macaca ; Medical sciences ; Medicin och hälsovetenskap ; Palatine Tonsil ; Palatine Tonsil - immunology ; Pharmacology. Drug treatments ; Receptors, Death Domain ; Receptors, Death Domain - genetics ; Receptors, Death Domain - metabolism ; RNA, Messenger ; RNA, Messenger - genetics ; Simian Acquired Immunodeficiency Syndrome ; Simian Acquired Immunodeficiency Syndrome - drug therapy ; Simian Acquired Immunodeficiency Syndrome - immunology ; TNF-Related Apoptosis-Inducing Ligand ; TNF-Related Apoptosis-Inducing Ligand - genetics ; TNF-Related Apoptosis-Inducing Ligand - metabolism ; Viral diseases ; Viral diseases of the lymphoid tissue and the blood. Aids</subject><ispartof>AIDS (London), 2009-01, Vol.23 (1), p.35-40</ispartof><rights>2009 INIST-CNRS</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c534t-f3b9ff0057ecda217a197e483cce9bb3e5635bee9630fce5429d3c5bc35dfe9d3</citedby><cites>FETCH-LOGICAL-c534t-f3b9ff0057ecda217a197e483cce9bb3e5635bee9630fce5429d3c5bc35dfe9d3</cites><orcidid>0000-0001-8114-8012</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,315,554,782,786,887,27931,27932</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21171909$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19050384$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-04204741$$DView record in HAL$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:118065827$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>HERBEUVAL, Jean-Philippe</creatorcontrib><creatorcontrib>NILSSON, Jakob</creatorcontrib><creatorcontrib>BOASSO, Adriano</creatorcontrib><creatorcontrib>HARDY, Andrew W</creatorcontrib><creatorcontrib>VACCARI, Monica</creatorcontrib><creatorcontrib>CECCHINATO, Valentina</creatorcontrib><creatorcontrib>VALERI, Valerio</creatorcontrib><creatorcontrib>FRANCHINI, Genoveffa</creatorcontrib><creatorcontrib>ANDERSSON, Jan</creatorcontrib><creatorcontrib>SHEARER, Gene M</creatorcontrib><title>HAART reduces death ligand but not death receptors in lymphoid tissue of HIV-infected patients and simian immunodeficiency virus-infected macaques</title><title>AIDS (London)</title><addtitle>AIDS</addtitle><description>To determine how antiretroviral therapy (ART) or HAART affects the expression of apoptotic ligands and their death receptors in the blood and lymphoid tissues of HIV-infected patients and simian immunodeficiency virus-infected macaques.
We analyzed the mRNA expression of death molecules [tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and FasL] and their receptors (DR5 and Fas) in blood and tonsils from HIV-infected patients (HIV positive), HIV-infected patients receiving HAART and HIV-uninfected (HIV negative) donors in a cross-sectional study. We comparatively analyzed mRNA expression of TRAIL and DR5 in blood and lymph nodes collected longitudinally from simian immunodeficiency virus-infected macaques before and after ART.
Expression of TRAIL, FasL, DR5 and Fas was elevated in circulating CD4 T cells from a group of HIV-positive patients as compared with that from both HIV-negative donors and HAART patients. In a different study group, TRAIL, FasL, DR5 and Fas were increased in tonsils of HIV-positive patients as compared with HIV-negative donors and HAART patients. However, tonsils from HAART patients showed reduced expression of TRAIL and FasL but not DR5 and Fas as compared with HIV-positive patients. Similarly, data obtained in a longitudinal study of simian immunodeficiency virus-infected macaques showed that ART reduced both TRAIL and DR5 in peripheral blood but only TRAIL and not DR5 in lymph nodes from the same animals.
These findings suggest that HAART or ART is ineffective in reducing the expression of apoptotic death receptors in lymphoid tissue. However, analysis limited to blood leukocytes may not reveal such a defect. Our results highlight the persistence of an underlying immunologic condition that may prevent therapy-induced restoration of CD4 T cells in lymphoid tissue.</description><subject>Animals</subject><subject>Anti-HIV Agents</subject><subject>Anti-HIV Agents - pharmacology</subject><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents</subject><subject>Antiretroviral Therapy, Highly Active</subject><subject>Antiviral agents</subject><subject>Biological and medical sciences</subject><subject>Cross-Sectional Studies</subject><subject>Fas Ligand Protein</subject><subject>Fas Ligand Protein - genetics</subject><subject>Fas Ligand Protein - metabolism</subject><subject>Gene Expression Regulation</subject><subject>Gene Expression Regulation - drug effects</subject><subject>HIV Infections</subject><subject>HIV Infections - drug therapy</subject><subject>HIV Infections - immunology</subject><subject>Human immunodeficiency virus</subject><subject>Human viral diseases</subject><subject>Humans</subject><subject>Immunodeficiencies</subject><subject>Immunodeficiencies. Immunoglobulinopathies</subject><subject>Immunopathology</subject><subject>Infectious diseases</subject><subject>Life Sciences</subject><subject>Lymph Nodes</subject><subject>Lymph Nodes - immunology</subject><subject>Lymphoid Tissue</subject><subject>Lymphoid Tissue - immunology</subject><subject>Macaca</subject><subject>Medical sciences</subject><subject>Medicin och hälsovetenskap</subject><subject>Palatine Tonsil</subject><subject>Palatine Tonsil - immunology</subject><subject>Pharmacology. Drug treatments</subject><subject>Receptors, Death Domain</subject><subject>Receptors, Death Domain - genetics</subject><subject>Receptors, Death Domain - metabolism</subject><subject>RNA, Messenger</subject><subject>RNA, Messenger - genetics</subject><subject>Simian Acquired Immunodeficiency Syndrome</subject><subject>Simian Acquired Immunodeficiency Syndrome - drug therapy</subject><subject>Simian Acquired Immunodeficiency Syndrome - immunology</subject><subject>TNF-Related Apoptosis-Inducing Ligand</subject><subject>TNF-Related Apoptosis-Inducing Ligand - genetics</subject><subject>TNF-Related Apoptosis-Inducing Ligand - metabolism</subject><subject>Viral diseases</subject><subject>Viral diseases of the lymphoid tissue and the blood. Aids</subject><issn>0269-9370</issn><issn>1473-5571</issn><issn>1473-5571</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>D8T</sourceid><recordid>eNp1kl1rFDEUhoModlv9ByK5UejF1GQymUwul1bdwoIo1duQjxM3Ol8mM5X9G_5is-zYRcGrHE6e54WEF6EXlFxRIsWbj-ubK2IIZcDKhlFrJBGP0IpWghWcC_oYrUhZy0IyQc7QeUrfCCGcNM1TdEZlnlhTrdCvzXr96Q5HcLOFhB3oaYfb8FX3Dpt5wv0wLcsIFsZpiAmHHrf7btwNweEppDQDHjze3H4pQu_BTuDwqKcA_ZTwISeFLugeh66b-8GBDzbf2T2-D3FOJ6fTVv-YIT1DT7xuEzxfzgv0-d3bu-tNsf3w_vZ6vS0sZ9VUeGak9_lJAqzTJRWaSgFVw6wFaQwDXjNuAGTNiLfAq1I6ZrmxjDsPeb5AxTE3_YRxNmqModNxrwYd1LL6nidQvCaSN5mX_-XHOLiT9EektCE1b0qR3cuju9PtX-JmvVWHHalKUomK3tPMvj6yOfTwH5PqQrLQtrqHYU6qJGVTc0oyWB1BG4eUIviHZErUoSMqd0T925GsvVzyZ9OBO0lLKTLwagF0srr1Ufc2pAeupFRkVrLf32PJpA</recordid><startdate>20090102</startdate><enddate>20090102</enddate><creator>HERBEUVAL, Jean-Philippe</creator><creator>NILSSON, Jakob</creator><creator>BOASSO, Adriano</creator><creator>HARDY, Andrew W</creator><creator>VACCARI, Monica</creator><creator>CECCHINATO, Valentina</creator><creator>VALERI, Valerio</creator><creator>FRANCHINI, Genoveffa</creator><creator>ANDERSSON, Jan</creator><creator>SHEARER, Gene M</creator><general>Lippincott Williams & Wilkins</general><general>Wolters Kluwer</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7U9</scope><scope>H94</scope><scope>1XC</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>D8T</scope><scope>ZZAVC</scope><orcidid>https://orcid.org/0000-0001-8114-8012</orcidid></search><sort><creationdate>20090102</creationdate><title>HAART reduces death ligand but not death receptors in lymphoid tissue of HIV-infected patients and simian immunodeficiency virus-infected macaques</title><author>HERBEUVAL, Jean-Philippe ; NILSSON, Jakob ; BOASSO, Adriano ; HARDY, Andrew W ; VACCARI, Monica ; CECCHINATO, Valentina ; VALERI, Valerio ; FRANCHINI, Genoveffa ; ANDERSSON, Jan ; SHEARER, Gene M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c534t-f3b9ff0057ecda217a197e483cce9bb3e5635bee9630fce5429d3c5bc35dfe9d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Animals</topic><topic>Anti-HIV Agents</topic><topic>Anti-HIV Agents - pharmacology</topic><topic>Antibiotics. Antiinfectious agents. Antiparasitic agents</topic><topic>Antiretroviral Therapy, Highly Active</topic><topic>Antiviral agents</topic><topic>Biological and medical sciences</topic><topic>Cross-Sectional Studies</topic><topic>Fas Ligand Protein</topic><topic>Fas Ligand Protein - genetics</topic><topic>Fas Ligand Protein - metabolism</topic><topic>Gene Expression Regulation</topic><topic>Gene Expression Regulation - drug effects</topic><topic>HIV Infections</topic><topic>HIV Infections - drug therapy</topic><topic>HIV Infections - immunology</topic><topic>Human immunodeficiency virus</topic><topic>Human viral diseases</topic><topic>Humans</topic><topic>Immunodeficiencies</topic><topic>Immunodeficiencies. Immunoglobulinopathies</topic><topic>Immunopathology</topic><topic>Infectious diseases</topic><topic>Life Sciences</topic><topic>Lymph Nodes</topic><topic>Lymph Nodes - immunology</topic><topic>Lymphoid Tissue</topic><topic>Lymphoid Tissue - immunology</topic><topic>Macaca</topic><topic>Medical sciences</topic><topic>Medicin och hälsovetenskap</topic><topic>Palatine Tonsil</topic><topic>Palatine Tonsil - immunology</topic><topic>Pharmacology. Drug treatments</topic><topic>Receptors, Death Domain</topic><topic>Receptors, Death Domain - genetics</topic><topic>Receptors, Death Domain - metabolism</topic><topic>RNA, Messenger</topic><topic>RNA, Messenger - genetics</topic><topic>Simian Acquired Immunodeficiency Syndrome</topic><topic>Simian Acquired Immunodeficiency Syndrome - drug therapy</topic><topic>Simian Acquired Immunodeficiency Syndrome - immunology</topic><topic>TNF-Related Apoptosis-Inducing Ligand</topic><topic>TNF-Related Apoptosis-Inducing Ligand - genetics</topic><topic>TNF-Related Apoptosis-Inducing Ligand - metabolism</topic><topic>Viral diseases</topic><topic>Viral diseases of the lymphoid tissue and the blood. Aids</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>HERBEUVAL, Jean-Philippe</creatorcontrib><creatorcontrib>NILSSON, Jakob</creatorcontrib><creatorcontrib>BOASSO, Adriano</creatorcontrib><creatorcontrib>HARDY, Andrew W</creatorcontrib><creatorcontrib>VACCARI, Monica</creatorcontrib><creatorcontrib>CECCHINATO, Valentina</creatorcontrib><creatorcontrib>VALERI, Valerio</creatorcontrib><creatorcontrib>FRANCHINI, Genoveffa</creatorcontrib><creatorcontrib>ANDERSSON, Jan</creatorcontrib><creatorcontrib>SHEARER, Gene M</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Freely available online</collection><collection>SwePub Articles full text</collection><jtitle>AIDS (London)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>HERBEUVAL, Jean-Philippe</au><au>NILSSON, Jakob</au><au>BOASSO, Adriano</au><au>HARDY, Andrew W</au><au>VACCARI, Monica</au><au>CECCHINATO, Valentina</au><au>VALERI, Valerio</au><au>FRANCHINI, Genoveffa</au><au>ANDERSSON, Jan</au><au>SHEARER, Gene M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>HAART reduces death ligand but not death receptors in lymphoid tissue of HIV-infected patients and simian immunodeficiency virus-infected macaques</atitle><jtitle>AIDS (London)</jtitle><addtitle>AIDS</addtitle><date>2009-01-02</date><risdate>2009</risdate><volume>23</volume><issue>1</issue><spage>35</spage><epage>40</epage><pages>35-40</pages><issn>0269-9370</issn><issn>1473-5571</issn><eissn>1473-5571</eissn><abstract>To determine how antiretroviral therapy (ART) or HAART affects the expression of apoptotic ligands and their death receptors in the blood and lymphoid tissues of HIV-infected patients and simian immunodeficiency virus-infected macaques.
We analyzed the mRNA expression of death molecules [tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and FasL] and their receptors (DR5 and Fas) in blood and tonsils from HIV-infected patients (HIV positive), HIV-infected patients receiving HAART and HIV-uninfected (HIV negative) donors in a cross-sectional study. We comparatively analyzed mRNA expression of TRAIL and DR5 in blood and lymph nodes collected longitudinally from simian immunodeficiency virus-infected macaques before and after ART.
Expression of TRAIL, FasL, DR5 and Fas was elevated in circulating CD4 T cells from a group of HIV-positive patients as compared with that from both HIV-negative donors and HAART patients. In a different study group, TRAIL, FasL, DR5 and Fas were increased in tonsils of HIV-positive patients as compared with HIV-negative donors and HAART patients. However, tonsils from HAART patients showed reduced expression of TRAIL and FasL but not DR5 and Fas as compared with HIV-positive patients. Similarly, data obtained in a longitudinal study of simian immunodeficiency virus-infected macaques showed that ART reduced both TRAIL and DR5 in peripheral blood but only TRAIL and not DR5 in lymph nodes from the same animals.
These findings suggest that HAART or ART is ineffective in reducing the expression of apoptotic death receptors in lymphoid tissue. However, analysis limited to blood leukocytes may not reveal such a defect. Our results highlight the persistence of an underlying immunologic condition that may prevent therapy-induced restoration of CD4 T cells in lymphoid tissue.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>19050384</pmid><doi>10.1097/QAD.0b013e32831cb907</doi><tpages>6</tpages><orcidid>https://orcid.org/0000-0001-8114-8012</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | AIDS (London), 2009-01, Vol.23 (1), p.35-40 |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; SWEPUB Freely available online; Journals@Ovid Complete |
| subjects | Animals Anti-HIV Agents Anti-HIV Agents - pharmacology Antibiotics. Antiinfectious agents. Antiparasitic agents Antiretroviral Therapy, Highly Active Antiviral agents Biological and medical sciences Cross-Sectional Studies Fas Ligand Protein Fas Ligand Protein - genetics Fas Ligand Protein - metabolism Gene Expression Regulation Gene Expression Regulation - drug effects HIV Infections HIV Infections - drug therapy HIV Infections - immunology Human immunodeficiency virus Human viral diseases Humans Immunodeficiencies Immunodeficiencies. Immunoglobulinopathies Immunopathology Infectious diseases Life Sciences Lymph Nodes Lymph Nodes - immunology Lymphoid Tissue Lymphoid Tissue - immunology Macaca Medical sciences Medicin och hälsovetenskap Palatine Tonsil Palatine Tonsil - immunology Pharmacology. Drug treatments Receptors, Death Domain Receptors, Death Domain - genetics Receptors, Death Domain - metabolism RNA, Messenger RNA, Messenger - genetics Simian Acquired Immunodeficiency Syndrome Simian Acquired Immunodeficiency Syndrome - drug therapy Simian Acquired Immunodeficiency Syndrome - immunology TNF-Related Apoptosis-Inducing Ligand TNF-Related Apoptosis-Inducing Ligand - genetics TNF-Related Apoptosis-Inducing Ligand - metabolism Viral diseases Viral diseases of the lymphoid tissue and the blood. Aids |
| title | HAART reduces death ligand but not death receptors in lymphoid tissue of HIV-infected patients and simian immunodeficiency virus-infected macaques |
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