Adipose Tissue is Enriched for Activated and Late-Differentiated CD8+ T Cells and Shows Distinct CD8+ Receptor Usage, Compared With Blood in HIV-Infected Persons
BACKGROUND:Adverse viral and medication effects on adipose tissue contribute to the development of metabolic disease in HIV-infected persons, but T cells also have a central role modulating local inflammation and adipocyte function. We sought to characterize potentially proinflammatory T-cell popula...
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| Veröffentlicht in: | Journal of acquired immune deficiency syndromes (1999) 2018-02, Vol.77 (2), p.e14-e21 |
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| container_title | Journal of acquired immune deficiency syndromes (1999) |
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| creator | Koethe, John R McDonnell, Wyatt Kennedy, Arion Abana, Chike O Pilkinton, Mark Setliff, Ian Georgiev, Ivelin Barnett, Louise Hager, Cindy C Smith, Rita Kalams, Spyros A Hasty, Alyssa Mallal, Simon |
| description | BACKGROUND:Adverse viral and medication effects on adipose tissue contribute to the development of metabolic disease in HIV-infected persons, but T cells also have a central role modulating local inflammation and adipocyte function. We sought to characterize potentially proinflammatory T-cell populations in adipose tissue among persons on long-term antiretroviral therapy and assess whether adipose tissue CD8 T cells represent an expanded, oligoclonal population.
METHODS:We recruited 10 HIV-infected, non-diabetic, overweight or obese adults on efavirenz, tenofovir, and emtricitabine for >4 years with consistent viral suppression. We collected fasting blood and subcutaneous abdominal adipose tissue to measure the percentage of CD4 and CD8 T cells expressing activation, exhaustion, late differentiation/senescence, and memory surface markers. We performed T-cell receptor (TCR) sequencing on sorted CD8 cells. We compared the proportion of each T-cell subset and the TCR repertoire diversity, in blood versus adipose tissue.
RESULTS:Adipose tissue had a higher percentage of CD3CD8 T cells compared with blood (61.0% vs. 51.7%, P < 0.01) and was enriched for both activated CD8HLA-DR T cells (5.5% vs. 0.9%, P < 0.01) and late-differentiated CD8CD57 T cells (37.4% vs. 22.7%, P < 0.01). Adipose tissue CD8 T cells displayed distinct TCRβ V and J gene usage, and the Shannon Entropy index, a measure of overall TCRβ repertoire diversity, was lower compared with blood (4.39 vs. 4.46; P = 0.05).
CONCLUSIONS:Adipose tissue is enriched for activated and late-differentiated CD8 T cells with distinct TCR usage. These cells may contribute to tissue inflammation and impaired adipocyte fitness in HIV-infected persons. |
| doi_str_mv | 10.1097/QAI.0000000000001573 |
| format | Article |
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METHODS:We recruited 10 HIV-infected, non-diabetic, overweight or obese adults on efavirenz, tenofovir, and emtricitabine for >4 years with consistent viral suppression. We collected fasting blood and subcutaneous abdominal adipose tissue to measure the percentage of CD4 and CD8 T cells expressing activation, exhaustion, late differentiation/senescence, and memory surface markers. We performed T-cell receptor (TCR) sequencing on sorted CD8 cells. We compared the proportion of each T-cell subset and the TCR repertoire diversity, in blood versus adipose tissue.
RESULTS:Adipose tissue had a higher percentage of CD3CD8 T cells compared with blood (61.0% vs. 51.7%, P < 0.01) and was enriched for both activated CD8HLA-DR T cells (5.5% vs. 0.9%, P < 0.01) and late-differentiated CD8CD57 T cells (37.4% vs. 22.7%, P < 0.01). Adipose tissue CD8 T cells displayed distinct TCRβ V and J gene usage, and the Shannon Entropy index, a measure of overall TCRβ repertoire diversity, was lower compared with blood (4.39 vs. 4.46; P = 0.05).
CONCLUSIONS:Adipose tissue is enriched for activated and late-differentiated CD8 T cells with distinct TCR usage. These cells may contribute to tissue inflammation and impaired adipocyte fitness in HIV-infected persons.</description><identifier>ISSN: 1525-4135</identifier><identifier>EISSN: 1944-7884</identifier><identifier>DOI: 10.1097/QAI.0000000000001573</identifier><identifier>PMID: 29040163</identifier><language>eng</language><publisher>United States: Copyright Wolters Kluwer Health, Inc. All rights reserved</publisher><subject>Adipose tissue ; Adipose Tissue - pathology ; Adult ; Adults ; Anti-HIV Agents - therapeutic use ; Antiretroviral agents ; Antiretroviral drugs ; Antiretroviral therapy ; Blood ; Blood Cells ; Body weight ; CD3 antigen ; CD4 antigen ; CD57 antigen ; CD8 antigen ; CD8-Positive T-Lymphocytes - chemistry ; CD8-Positive T-Lymphocytes - immunology ; Cell activation ; Cohort Studies ; Diabetes mellitus ; Drugs ; Efavirenz ; Emtricitabine ; Enrichment ; Entropy (Information theory) ; Exhaustion ; Female ; Fitness ; Histocompatibility antigen HLA ; HIV ; HIV Infections - drug therapy ; HIV Infections - pathology ; Human immunodeficiency virus ; Humans ; Inflammation ; J gene ; Lymphocytes ; Lymphocytes T ; Male ; Memory cells ; Metabolic disorders ; Middle Aged ; Overweight ; Receptors, Antigen, T-Cell - analysis ; Senescence ; Sequence Analysis, DNA ; Surface markers ; Sustained Virologic Response ; T cell receptors ; T-Lymphocyte Subsets - chemistry ; T-Lymphocyte Subsets - immunology ; Tenofovir ; Tissues</subject><ispartof>Journal of acquired immune deficiency syndromes (1999), 2018-02, Vol.77 (2), p.e14-e21</ispartof><rights>Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.</rights><rights>Copyright Lippincott Williams & Wilkins Ovid Technologies Feb 1, 2018</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4303-437bfda9849368ec681ed554d21e635302f1993e9fa0e5203693ce59ae37c0dc3</citedby><cites>FETCH-LOGICAL-c4303-437bfda9849368ec681ed554d21e635302f1993e9fa0e5203693ce59ae37c0dc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29040163$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Koethe, John R</creatorcontrib><creatorcontrib>McDonnell, Wyatt</creatorcontrib><creatorcontrib>Kennedy, Arion</creatorcontrib><creatorcontrib>Abana, Chike O</creatorcontrib><creatorcontrib>Pilkinton, Mark</creatorcontrib><creatorcontrib>Setliff, Ian</creatorcontrib><creatorcontrib>Georgiev, Ivelin</creatorcontrib><creatorcontrib>Barnett, Louise</creatorcontrib><creatorcontrib>Hager, Cindy C</creatorcontrib><creatorcontrib>Smith, Rita</creatorcontrib><creatorcontrib>Kalams, Spyros A</creatorcontrib><creatorcontrib>Hasty, Alyssa</creatorcontrib><creatorcontrib>Mallal, Simon</creatorcontrib><title>Adipose Tissue is Enriched for Activated and Late-Differentiated CD8+ T Cells and Shows Distinct CD8+ Receptor Usage, Compared With Blood in HIV-Infected Persons</title><title>Journal of acquired immune deficiency syndromes (1999)</title><addtitle>J Acquir Immune Defic Syndr</addtitle><description>BACKGROUND:Adverse viral and medication effects on adipose tissue contribute to the development of metabolic disease in HIV-infected persons, but T cells also have a central role modulating local inflammation and adipocyte function. We sought to characterize potentially proinflammatory T-cell populations in adipose tissue among persons on long-term antiretroviral therapy and assess whether adipose tissue CD8 T cells represent an expanded, oligoclonal population.
METHODS:We recruited 10 HIV-infected, non-diabetic, overweight or obese adults on efavirenz, tenofovir, and emtricitabine for >4 years with consistent viral suppression. We collected fasting blood and subcutaneous abdominal adipose tissue to measure the percentage of CD4 and CD8 T cells expressing activation, exhaustion, late differentiation/senescence, and memory surface markers. We performed T-cell receptor (TCR) sequencing on sorted CD8 cells. We compared the proportion of each T-cell subset and the TCR repertoire diversity, in blood versus adipose tissue.
RESULTS:Adipose tissue had a higher percentage of CD3CD8 T cells compared with blood (61.0% vs. 51.7%, P < 0.01) and was enriched for both activated CD8HLA-DR T cells (5.5% vs. 0.9%, P < 0.01) and late-differentiated CD8CD57 T cells (37.4% vs. 22.7%, P < 0.01). Adipose tissue CD8 T cells displayed distinct TCRβ V and J gene usage, and the Shannon Entropy index, a measure of overall TCRβ repertoire diversity, was lower compared with blood (4.39 vs. 4.46; P = 0.05).
CONCLUSIONS:Adipose tissue is enriched for activated and late-differentiated CD8 T cells with distinct TCR usage. These cells may contribute to tissue inflammation and impaired adipocyte fitness in HIV-infected persons.</description><subject>Adipose tissue</subject><subject>Adipose Tissue - pathology</subject><subject>Adult</subject><subject>Adults</subject><subject>Anti-HIV Agents - therapeutic use</subject><subject>Antiretroviral agents</subject><subject>Antiretroviral drugs</subject><subject>Antiretroviral therapy</subject><subject>Blood</subject><subject>Blood Cells</subject><subject>Body weight</subject><subject>CD3 antigen</subject><subject>CD4 antigen</subject><subject>CD57 antigen</subject><subject>CD8 antigen</subject><subject>CD8-Positive T-Lymphocytes - chemistry</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>Cell activation</subject><subject>Cohort Studies</subject><subject>Diabetes mellitus</subject><subject>Drugs</subject><subject>Efavirenz</subject><subject>Emtricitabine</subject><subject>Enrichment</subject><subject>Entropy (Information theory)</subject><subject>Exhaustion</subject><subject>Female</subject><subject>Fitness</subject><subject>Histocompatibility antigen HLA</subject><subject>HIV</subject><subject>HIV Infections - drug therapy</subject><subject>HIV Infections - pathology</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Inflammation</subject><subject>J gene</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Male</subject><subject>Memory cells</subject><subject>Metabolic disorders</subject><subject>Middle Aged</subject><subject>Overweight</subject><subject>Receptors, Antigen, T-Cell - analysis</subject><subject>Senescence</subject><subject>Sequence Analysis, DNA</subject><subject>Surface markers</subject><subject>Sustained Virologic Response</subject><subject>T cell receptors</subject><subject>T-Lymphocyte Subsets - chemistry</subject><subject>T-Lymphocyte Subsets - immunology</subject><subject>Tenofovir</subject><subject>Tissues</subject><issn>1525-4135</issn><issn>1944-7884</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kdFuFCEUhonR2Fp9A2NIvNRpYYCZ4XI7W9tNNrHqVi8nFA4OdXYYgXHj4_impd1qjBdywznw_f8J_Ai9pOSYElmffFisjslfi4qaPUKHVHJe1E3DH-dalKLglIkD9CzGm8xUnMun6KCUhOeGHaJfC-MmHwFvXIwzYBfx2Ric7sFg6wNe6OR-qJQ7NRq8zlWxdNZCgDG5-_N22bzBG9zCMMR76FPvdxEvXUxu1Gl__xE0TCn7XUX1Fd7i1m8nFbL6i0s9Ph28N9iN-GL1uViNFvSd8SWE6Mf4HD2xaojw4mE_QlfvzjbtRbF-f75qF-tCc0ZYwVl9bY2SDZesakBXDQUjBDclhYoJRkpLpWQgrSIgSsIqyTQIqYDVmhjNjtDrve8U_PcZYupu_BzGPLLLwvzlgvAyU3xP6eBjDGC7KbitCj87Srq7XLqcS_dvLln26sF8vt6C-SP6HUQGmj2w80PKD_82zDsIXQ9qSP3_vW8BRd6X2g</recordid><startdate>20180201</startdate><enddate>20180201</enddate><creator>Koethe, John R</creator><creator>McDonnell, Wyatt</creator><creator>Kennedy, Arion</creator><creator>Abana, Chike O</creator><creator>Pilkinton, Mark</creator><creator>Setliff, Ian</creator><creator>Georgiev, Ivelin</creator><creator>Barnett, Louise</creator><creator>Hager, Cindy C</creator><creator>Smith, Rita</creator><creator>Kalams, Spyros A</creator><creator>Hasty, Alyssa</creator><creator>Mallal, Simon</creator><general>Copyright Wolters Kluwer Health, Inc. All rights reserved</general><general>Lippincott Williams & Wilkins Ovid Technologies</general><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>7T2</scope><scope>7T5</scope><scope>7TK</scope><scope>7U7</scope><scope>7U9</scope><scope>C1K</scope><scope>H94</scope><scope>K9.</scope></search><sort><creationdate>20180201</creationdate><title>Adipose Tissue is Enriched for Activated and Late-Differentiated CD8+ T Cells and Shows Distinct CD8+ Receptor Usage, Compared With Blood in HIV-Infected Persons</title><author>Koethe, John R ; McDonnell, Wyatt ; Kennedy, Arion ; Abana, Chike O ; Pilkinton, Mark ; Setliff, Ian ; Georgiev, Ivelin ; Barnett, Louise ; Hager, Cindy C ; Smith, Rita ; Kalams, Spyros A ; Hasty, Alyssa ; Mallal, Simon</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4303-437bfda9849368ec681ed554d21e635302f1993e9fa0e5203693ce59ae37c0dc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adipose tissue</topic><topic>Adipose Tissue - pathology</topic><topic>Adult</topic><topic>Adults</topic><topic>Anti-HIV Agents - therapeutic use</topic><topic>Antiretroviral agents</topic><topic>Antiretroviral drugs</topic><topic>Antiretroviral therapy</topic><topic>Blood</topic><topic>Blood Cells</topic><topic>Body weight</topic><topic>CD3 antigen</topic><topic>CD4 antigen</topic><topic>CD57 antigen</topic><topic>CD8 antigen</topic><topic>CD8-Positive T-Lymphocytes - chemistry</topic><topic>CD8-Positive T-Lymphocytes - immunology</topic><topic>Cell activation</topic><topic>Cohort Studies</topic><topic>Diabetes mellitus</topic><topic>Drugs</topic><topic>Efavirenz</topic><topic>Emtricitabine</topic><topic>Enrichment</topic><topic>Entropy (Information theory)</topic><topic>Exhaustion</topic><topic>Female</topic><topic>Fitness</topic><topic>Histocompatibility antigen HLA</topic><topic>HIV</topic><topic>HIV Infections - drug therapy</topic><topic>HIV Infections - pathology</topic><topic>Human immunodeficiency virus</topic><topic>Humans</topic><topic>Inflammation</topic><topic>J gene</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Male</topic><topic>Memory cells</topic><topic>Metabolic disorders</topic><topic>Middle Aged</topic><topic>Overweight</topic><topic>Receptors, Antigen, T-Cell - analysis</topic><topic>Senescence</topic><topic>Sequence Analysis, DNA</topic><topic>Surface markers</topic><topic>Sustained Virologic Response</topic><topic>T cell receptors</topic><topic>T-Lymphocyte Subsets - chemistry</topic><topic>T-Lymphocyte Subsets - immunology</topic><topic>Tenofovir</topic><topic>Tissues</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Koethe, John R</creatorcontrib><creatorcontrib>McDonnell, Wyatt</creatorcontrib><creatorcontrib>Kennedy, Arion</creatorcontrib><creatorcontrib>Abana, Chike O</creatorcontrib><creatorcontrib>Pilkinton, Mark</creatorcontrib><creatorcontrib>Setliff, Ian</creatorcontrib><creatorcontrib>Georgiev, Ivelin</creatorcontrib><creatorcontrib>Barnett, Louise</creatorcontrib><creatorcontrib>Hager, Cindy C</creatorcontrib><creatorcontrib>Smith, Rita</creatorcontrib><creatorcontrib>Kalams, Spyros A</creatorcontrib><creatorcontrib>Hasty, Alyssa</creatorcontrib><creatorcontrib>Mallal, Simon</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Health and Safety Science Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><jtitle>Journal of acquired immune deficiency syndromes (1999)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Koethe, John R</au><au>McDonnell, Wyatt</au><au>Kennedy, Arion</au><au>Abana, Chike O</au><au>Pilkinton, Mark</au><au>Setliff, Ian</au><au>Georgiev, Ivelin</au><au>Barnett, Louise</au><au>Hager, Cindy C</au><au>Smith, Rita</au><au>Kalams, Spyros A</au><au>Hasty, Alyssa</au><au>Mallal, Simon</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Adipose Tissue is Enriched for Activated and Late-Differentiated CD8+ T Cells and Shows Distinct CD8+ Receptor Usage, Compared With Blood in HIV-Infected Persons</atitle><jtitle>Journal of acquired immune deficiency syndromes (1999)</jtitle><addtitle>J Acquir Immune Defic Syndr</addtitle><date>2018-02-01</date><risdate>2018</risdate><volume>77</volume><issue>2</issue><spage>e14</spage><epage>e21</epage><pages>e14-e21</pages><issn>1525-4135</issn><eissn>1944-7884</eissn><abstract>BACKGROUND:Adverse viral and medication effects on adipose tissue contribute to the development of metabolic disease in HIV-infected persons, but T cells also have a central role modulating local inflammation and adipocyte function. We sought to characterize potentially proinflammatory T-cell populations in adipose tissue among persons on long-term antiretroviral therapy and assess whether adipose tissue CD8 T cells represent an expanded, oligoclonal population.
METHODS:We recruited 10 HIV-infected, non-diabetic, overweight or obese adults on efavirenz, tenofovir, and emtricitabine for >4 years with consistent viral suppression. We collected fasting blood and subcutaneous abdominal adipose tissue to measure the percentage of CD4 and CD8 T cells expressing activation, exhaustion, late differentiation/senescence, and memory surface markers. We performed T-cell receptor (TCR) sequencing on sorted CD8 cells. We compared the proportion of each T-cell subset and the TCR repertoire diversity, in blood versus adipose tissue.
RESULTS:Adipose tissue had a higher percentage of CD3CD8 T cells compared with blood (61.0% vs. 51.7%, P < 0.01) and was enriched for both activated CD8HLA-DR T cells (5.5% vs. 0.9%, P < 0.01) and late-differentiated CD8CD57 T cells (37.4% vs. 22.7%, P < 0.01). Adipose tissue CD8 T cells displayed distinct TCRβ V and J gene usage, and the Shannon Entropy index, a measure of overall TCRβ repertoire diversity, was lower compared with blood (4.39 vs. 4.46; P = 0.05).
CONCLUSIONS:Adipose tissue is enriched for activated and late-differentiated CD8 T cells with distinct TCR usage. These cells may contribute to tissue inflammation and impaired adipocyte fitness in HIV-infected persons.</abstract><cop>United States</cop><pub>Copyright Wolters Kluwer Health, Inc. All rights reserved</pub><pmid>29040163</pmid><doi>10.1097/QAI.0000000000001573</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Adipose tissue Adipose Tissue - pathology Adult Adults Anti-HIV Agents - therapeutic use Antiretroviral agents Antiretroviral drugs Antiretroviral therapy Blood Blood Cells Body weight CD3 antigen CD4 antigen CD57 antigen CD8 antigen CD8-Positive T-Lymphocytes - chemistry CD8-Positive T-Lymphocytes - immunology Cell activation Cohort Studies Diabetes mellitus Drugs Efavirenz Emtricitabine Enrichment Entropy (Information theory) Exhaustion Female Fitness Histocompatibility antigen HLA HIV HIV Infections - drug therapy HIV Infections - pathology Human immunodeficiency virus Humans Inflammation J gene Lymphocytes Lymphocytes T Male Memory cells Metabolic disorders Middle Aged Overweight Receptors, Antigen, T-Cell - analysis Senescence Sequence Analysis, DNA Surface markers Sustained Virologic Response T cell receptors T-Lymphocyte Subsets - chemistry T-Lymphocyte Subsets - immunology Tenofovir Tissues |
| title | Adipose Tissue is Enriched for Activated and Late-Differentiated CD8+ T Cells and Shows Distinct CD8+ Receptor Usage, Compared With Blood in HIV-Infected Persons |
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