Programmed death-1 expression on CD4+ and CD8+ T cells in treated and untreated HIV disease
BACKGROUND:There is intense interest in the role of programmed death 1 (PD-1) in causing persistent T-cell dysfunction in HIV infection. However, the impact of HIV infection and antiretroviral treatment (ART) on the expression of PD-1 on T cells is still poorly defined. METHODS:PD-1 was measured lon...
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| Veröffentlicht in: | AIDS (London) 2014-07, Vol.28 (12), p.1749-1758 |
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| creator | Cockerham, Leslie R Jain, Vivek Sinclair, Elizabeth Glidden, David V Hartogenesis, Wendy Hatano, Hiroyu Hunt, Peter W Martin, Jeffrey N Pilcher, Christopher D Sekaly, Rafick McCune, Joseph M Hecht, Frederick M Deeks, Steven G |
| description | BACKGROUND:There is intense interest in the role of programmed death 1 (PD-1) in causing persistent T-cell dysfunction in HIV infection. However, the impact of HIV infection and antiretroviral treatment (ART) on the expression of PD-1 on T cells is still poorly defined.
METHODS:PD-1 was measured longitudinally in a cohort of recently HIV-infected individuals (n = 121) who started ART early ( |
| doi_str_mv | 10.1097/QAD.0000000000000314 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4206412</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1544738967</sourcerecordid><originalsourceid>FETCH-LOGICAL-c6084-5530f2787eb417fa60999f35f04cff1b1c84b26b3b3619ccd10138145e5e82a43</originalsourceid><addsrcrecordid>eNp9kd9P2zAQxy0Ego7tP5gmv0xCQmG-2Imdl0lVuwESEpsEvOzBcpwzDaRJsRN-_Pdz1Ra6PWBZ8ln3ufP3_CXkM7ATYIX89ns8PWHbi4PYISMQkidZJmGXjFiaF0nBJTsgH0K4i0zGlNonB6lQEkSWjcifX7679WY-x4pWaPpZAhSfFx5DqLuWxj2ZimNq2ioG6pheUYtNE2jd0t5HPpYtc0O7uZ2d39CqDmgCfiR7zjQBP63PQ3L988fV5Cy5uDw9n4wvEpszJaJYzlwqlcRSgHQmZ0VROJ45JqxzUIJVokzzkpc8h8LaChhwFeVjhio1gh-S76u-i6GMc1iMYkyjF76eG_-iO1PrfzNtPdO33aMWKcsFpLHB0bqB7x4GDL2e12E5p2mxG4KGTMRfVUUuIypWqPVdCB7d6zPA9NIXHX3R__sSy75sS3wt2hgRga9rwARrGudNa-vwximZglIscmrFPXVNjz7cN8MTej1D0_Sz9zX8Bf4mpI0</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1544738967</pqid></control><display><type>article</type><title>Programmed death-1 expression on CD4+ and CD8+ T cells in treated and untreated HIV disease</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Journals@Ovid Complete</source><creator>Cockerham, Leslie R ; Jain, Vivek ; Sinclair, Elizabeth ; Glidden, David V ; Hartogenesis, Wendy ; Hatano, Hiroyu ; Hunt, Peter W ; Martin, Jeffrey N ; Pilcher, Christopher D ; Sekaly, Rafick ; McCune, Joseph M ; Hecht, Frederick M ; Deeks, Steven G</creator><creatorcontrib>Cockerham, Leslie R ; Jain, Vivek ; Sinclair, Elizabeth ; Glidden, David V ; Hartogenesis, Wendy ; Hatano, Hiroyu ; Hunt, Peter W ; Martin, Jeffrey N ; Pilcher, Christopher D ; Sekaly, Rafick ; McCune, Joseph M ; Hecht, Frederick M ; Deeks, Steven G</creatorcontrib><description>BACKGROUND:There is intense interest in the role of programmed death 1 (PD-1) in causing persistent T-cell dysfunction in HIV infection. However, the impact of HIV infection and antiretroviral treatment (ART) on the expression of PD-1 on T cells is still poorly defined.
METHODS:PD-1 was measured longitudinally in a cohort of recently HIV-infected individuals (n = 121) who started ART early (<6 months after infection) vs. later (≥2 years after infection). PD-1 was also measured cross-sectionally in a diverse cohort of chronically HIV-infected adults (n = 206).
RESULTS:PD-1 expression levels were high on CD8 T cells during early HIV infection. PD-1 levels increased on both CD4 and CD8 T cells populations in those who delayed therapy (11 and 10%/year, respectively). PD-1 levels declined and were similar in those treated early vs. late after 1 year of ART. In both cohorts, PD-1 expression on CD4 T cells was associated with CD4 T-cell activation (CD38HLA-DR) and inversely with CD4 cell count. In contrast, PD-1 expression on CD8 T cells was most strongly associated with CD8 T-cell activation and with plasma viral load in viremic individuals.
CONCLUSION:Across two large cohorts of untreated and treated individuals, we found consistent associations between HIV RNA levels, CD8 T-cell activation and PD-1 expression on CD8 T cells. In contrast, CD4 T-cell counts and CD4 T-cell activation were more consistent correlates of PD-1 expression on CD4 T cells. PD-1 expression appears to be driven by both direct antigen and homeostatic pathways.</description><identifier>ISSN: 0269-9370</identifier><identifier>EISSN: 1473-5571</identifier><identifier>DOI: 10.1097/QAD.0000000000000314</identifier><identifier>PMID: 24871455</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins, Inc</publisher><subject>Adult ; AIDS/HIV ; Anti-Retroviral Agents - therapeutic use ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; Antiviral agents ; Biological and medical sciences ; CD4-Positive T-Lymphocytes - chemistry ; CD8-Positive T-Lymphocytes - chemistry ; CD8-Positive T-Lymphocytes - immunology ; Cohort Studies ; Female ; HIV Infections - drug therapy ; HIV Infections - pathology ; Human viral diseases ; Humans ; Immunodeficiencies ; Immunodeficiencies. Immunoglobulinopathies ; Immunopathology ; Infectious diseases ; Longitudinal Studies ; Lymphocyte Activation ; Male ; Medical sciences ; Middle Aged ; Pharmacology. Drug treatments ; Programmed Cell Death 1 Receptor - analysis ; Prospective Studies ; RNA, Viral - blood ; Viral diseases ; Viral diseases of the lymphoid tissue and the blood. Aids ; Viral Load</subject><ispartof>AIDS (London), 2014-07, Vol.28 (12), p.1749-1758</ispartof><rights>2014 Lippincott Williams & Wilkins, Inc.</rights><rights>2015 INIST-CNRS</rights><rights>2014 Wolters Kluwer Health | Lippincott Williams & Wilkins 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c6084-5530f2787eb417fa60999f35f04cff1b1c84b26b3b3619ccd10138145e5e82a43</citedby><cites>FETCH-LOGICAL-c6084-5530f2787eb417fa60999f35f04cff1b1c84b26b3b3619ccd10138145e5e82a43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=28721880$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24871455$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cockerham, Leslie R</creatorcontrib><creatorcontrib>Jain, Vivek</creatorcontrib><creatorcontrib>Sinclair, Elizabeth</creatorcontrib><creatorcontrib>Glidden, David V</creatorcontrib><creatorcontrib>Hartogenesis, Wendy</creatorcontrib><creatorcontrib>Hatano, Hiroyu</creatorcontrib><creatorcontrib>Hunt, Peter W</creatorcontrib><creatorcontrib>Martin, Jeffrey N</creatorcontrib><creatorcontrib>Pilcher, Christopher D</creatorcontrib><creatorcontrib>Sekaly, Rafick</creatorcontrib><creatorcontrib>McCune, Joseph M</creatorcontrib><creatorcontrib>Hecht, Frederick M</creatorcontrib><creatorcontrib>Deeks, Steven G</creatorcontrib><title>Programmed death-1 expression on CD4+ and CD8+ T cells in treated and untreated HIV disease</title><title>AIDS (London)</title><addtitle>AIDS</addtitle><description>BACKGROUND:There is intense interest in the role of programmed death 1 (PD-1) in causing persistent T-cell dysfunction in HIV infection. However, the impact of HIV infection and antiretroviral treatment (ART) on the expression of PD-1 on T cells is still poorly defined.
METHODS:PD-1 was measured longitudinally in a cohort of recently HIV-infected individuals (n = 121) who started ART early (<6 months after infection) vs. later (≥2 years after infection). PD-1 was also measured cross-sectionally in a diverse cohort of chronically HIV-infected adults (n = 206).
RESULTS:PD-1 expression levels were high on CD8 T cells during early HIV infection. PD-1 levels increased on both CD4 and CD8 T cells populations in those who delayed therapy (11 and 10%/year, respectively). PD-1 levels declined and were similar in those treated early vs. late after 1 year of ART. In both cohorts, PD-1 expression on CD4 T cells was associated with CD4 T-cell activation (CD38HLA-DR) and inversely with CD4 cell count. In contrast, PD-1 expression on CD8 T cells was most strongly associated with CD8 T-cell activation and with plasma viral load in viremic individuals.
CONCLUSION:Across two large cohorts of untreated and treated individuals, we found consistent associations between HIV RNA levels, CD8 T-cell activation and PD-1 expression on CD8 T cells. In contrast, CD4 T-cell counts and CD4 T-cell activation were more consistent correlates of PD-1 expression on CD4 T cells. PD-1 expression appears to be driven by both direct antigen and homeostatic pathways.</description><subject>Adult</subject><subject>AIDS/HIV</subject><subject>Anti-Retroviral Agents - therapeutic use</subject><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents</subject><subject>Antiviral agents</subject><subject>Biological and medical sciences</subject><subject>CD4-Positive T-Lymphocytes - chemistry</subject><subject>CD8-Positive T-Lymphocytes - chemistry</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>Cohort Studies</subject><subject>Female</subject><subject>HIV Infections - drug therapy</subject><subject>HIV Infections - pathology</subject><subject>Human viral diseases</subject><subject>Humans</subject><subject>Immunodeficiencies</subject><subject>Immunodeficiencies. Immunoglobulinopathies</subject><subject>Immunopathology</subject><subject>Infectious diseases</subject><subject>Longitudinal Studies</subject><subject>Lymphocyte Activation</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Pharmacology. Drug treatments</subject><subject>Programmed Cell Death 1 Receptor - analysis</subject><subject>Prospective Studies</subject><subject>RNA, Viral - blood</subject><subject>Viral diseases</subject><subject>Viral diseases of the lymphoid tissue and the blood. Aids</subject><subject>Viral Load</subject><issn>0269-9370</issn><issn>1473-5571</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kd9P2zAQxy0Ego7tP5gmv0xCQmG-2Imdl0lVuwESEpsEvOzBcpwzDaRJsRN-_Pdz1Ra6PWBZ8ln3ufP3_CXkM7ATYIX89ns8PWHbi4PYISMQkidZJmGXjFiaF0nBJTsgH0K4i0zGlNonB6lQEkSWjcifX7679WY-x4pWaPpZAhSfFx5DqLuWxj2ZimNq2ioG6pheUYtNE2jd0t5HPpYtc0O7uZ2d39CqDmgCfiR7zjQBP63PQ3L988fV5Cy5uDw9n4wvEpszJaJYzlwqlcRSgHQmZ0VROJ45JqxzUIJVokzzkpc8h8LaChhwFeVjhio1gh-S76u-i6GMc1iMYkyjF76eG_-iO1PrfzNtPdO33aMWKcsFpLHB0bqB7x4GDL2e12E5p2mxG4KGTMRfVUUuIypWqPVdCB7d6zPA9NIXHX3R__sSy75sS3wt2hgRga9rwARrGudNa-vwximZglIscmrFPXVNjz7cN8MTej1D0_Sz9zX8Bf4mpI0</recordid><startdate>20140731</startdate><enddate>20140731</enddate><creator>Cockerham, Leslie R</creator><creator>Jain, Vivek</creator><creator>Sinclair, Elizabeth</creator><creator>Glidden, David V</creator><creator>Hartogenesis, Wendy</creator><creator>Hatano, Hiroyu</creator><creator>Hunt, Peter W</creator><creator>Martin, Jeffrey N</creator><creator>Pilcher, Christopher D</creator><creator>Sekaly, Rafick</creator><creator>McCune, Joseph M</creator><creator>Hecht, Frederick M</creator><creator>Deeks, Steven G</creator><general>Lippincott Williams & Wilkins, Inc</general><general>Lippincott Williams & Wilkins</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20140731</creationdate><title>Programmed death-1 expression on CD4+ and CD8+ T cells in treated and untreated HIV disease</title><author>Cockerham, Leslie R ; Jain, Vivek ; Sinclair, Elizabeth ; Glidden, David V ; Hartogenesis, Wendy ; Hatano, Hiroyu ; Hunt, Peter W ; Martin, Jeffrey N ; Pilcher, Christopher D ; Sekaly, Rafick ; McCune, Joseph M ; Hecht, Frederick M ; Deeks, Steven G</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c6084-5530f2787eb417fa60999f35f04cff1b1c84b26b3b3619ccd10138145e5e82a43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adult</topic><topic>AIDS/HIV</topic><topic>Anti-Retroviral Agents - therapeutic use</topic><topic>Antibiotics. Antiinfectious agents. Antiparasitic agents</topic><topic>Antiviral agents</topic><topic>Biological and medical sciences</topic><topic>CD4-Positive T-Lymphocytes - chemistry</topic><topic>CD8-Positive T-Lymphocytes - chemistry</topic><topic>CD8-Positive T-Lymphocytes - immunology</topic><topic>Cohort Studies</topic><topic>Female</topic><topic>HIV Infections - drug therapy</topic><topic>HIV Infections - pathology</topic><topic>Human viral diseases</topic><topic>Humans</topic><topic>Immunodeficiencies</topic><topic>Immunodeficiencies. Immunoglobulinopathies</topic><topic>Immunopathology</topic><topic>Infectious diseases</topic><topic>Longitudinal Studies</topic><topic>Lymphocyte Activation</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Pharmacology. Drug treatments</topic><topic>Programmed Cell Death 1 Receptor - analysis</topic><topic>Prospective Studies</topic><topic>RNA, Viral - blood</topic><topic>Viral diseases</topic><topic>Viral diseases of the lymphoid tissue and the blood. Aids</topic><topic>Viral Load</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cockerham, Leslie R</creatorcontrib><creatorcontrib>Jain, Vivek</creatorcontrib><creatorcontrib>Sinclair, Elizabeth</creatorcontrib><creatorcontrib>Glidden, David V</creatorcontrib><creatorcontrib>Hartogenesis, Wendy</creatorcontrib><creatorcontrib>Hatano, Hiroyu</creatorcontrib><creatorcontrib>Hunt, Peter W</creatorcontrib><creatorcontrib>Martin, Jeffrey N</creatorcontrib><creatorcontrib>Pilcher, Christopher D</creatorcontrib><creatorcontrib>Sekaly, Rafick</creatorcontrib><creatorcontrib>McCune, Joseph M</creatorcontrib><creatorcontrib>Hecht, Frederick M</creatorcontrib><creatorcontrib>Deeks, Steven G</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>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>AIDS (London)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cockerham, Leslie R</au><au>Jain, Vivek</au><au>Sinclair, Elizabeth</au><au>Glidden, David V</au><au>Hartogenesis, Wendy</au><au>Hatano, Hiroyu</au><au>Hunt, Peter W</au><au>Martin, Jeffrey N</au><au>Pilcher, Christopher D</au><au>Sekaly, Rafick</au><au>McCune, Joseph M</au><au>Hecht, Frederick M</au><au>Deeks, Steven G</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Programmed death-1 expression on CD4+ and CD8+ T cells in treated and untreated HIV disease</atitle><jtitle>AIDS (London)</jtitle><addtitle>AIDS</addtitle><date>2014-07-31</date><risdate>2014</risdate><volume>28</volume><issue>12</issue><spage>1749</spage><epage>1758</epage><pages>1749-1758</pages><issn>0269-9370</issn><eissn>1473-5571</eissn><abstract>BACKGROUND:There is intense interest in the role of programmed death 1 (PD-1) in causing persistent T-cell dysfunction in HIV infection. However, the impact of HIV infection and antiretroviral treatment (ART) on the expression of PD-1 on T cells is still poorly defined.
METHODS:PD-1 was measured longitudinally in a cohort of recently HIV-infected individuals (n = 121) who started ART early (<6 months after infection) vs. later (≥2 years after infection). PD-1 was also measured cross-sectionally in a diverse cohort of chronically HIV-infected adults (n = 206).
RESULTS:PD-1 expression levels were high on CD8 T cells during early HIV infection. PD-1 levels increased on both CD4 and CD8 T cells populations in those who delayed therapy (11 and 10%/year, respectively). PD-1 levels declined and were similar in those treated early vs. late after 1 year of ART. In both cohorts, PD-1 expression on CD4 T cells was associated with CD4 T-cell activation (CD38HLA-DR) and inversely with CD4 cell count. In contrast, PD-1 expression on CD8 T cells was most strongly associated with CD8 T-cell activation and with plasma viral load in viremic individuals.
CONCLUSION:Across two large cohorts of untreated and treated individuals, we found consistent associations between HIV RNA levels, CD8 T-cell activation and PD-1 expression on CD8 T cells. In contrast, CD4 T-cell counts and CD4 T-cell activation were more consistent correlates of PD-1 expression on CD4 T cells. PD-1 expression appears to be driven by both direct antigen and homeostatic pathways.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins, Inc</pub><pmid>24871455</pmid><doi>10.1097/QAD.0000000000000314</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | AIDS (London), 2014-07, Vol.28 (12), p.1749-1758 |
| issn | 0269-9370 1473-5571 |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Journals@Ovid Complete |
| subjects | Adult AIDS/HIV Anti-Retroviral Agents - therapeutic use Antibiotics. Antiinfectious agents. Antiparasitic agents Antiviral agents Biological and medical sciences CD4-Positive T-Lymphocytes - chemistry CD8-Positive T-Lymphocytes - chemistry CD8-Positive T-Lymphocytes - immunology Cohort Studies Female HIV Infections - drug therapy HIV Infections - pathology Human viral diseases Humans Immunodeficiencies Immunodeficiencies. Immunoglobulinopathies Immunopathology Infectious diseases Longitudinal Studies Lymphocyte Activation Male Medical sciences Middle Aged Pharmacology. Drug treatments Programmed Cell Death 1 Receptor - analysis Prospective Studies RNA, Viral - blood Viral diseases Viral diseases of the lymphoid tissue and the blood. Aids Viral Load |
| title | Programmed death-1 expression on CD4+ and CD8+ T cells in treated and untreated HIV disease |
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