Restoration of the CD4 T Cell Compartment after Long-Term Highly Active Antiretroviral Therapy without Phenotypical Signs of Accelerated Immunological Aging
It remains uncertain whether full T cell reconstitution can be established in HIV-infected children and adults with long-term sustained virological control by highly active antiretroviral therapy (HAART). In this study, we comprehensively analyzed various phenotypical markers of CD4 T cell recovery....
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| Veröffentlicht in: | The Journal of immunology (1950) 2008-07, Vol.181 (2), p.1573-1581 |
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| container_title | The Journal of immunology (1950) |
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| creator | Vrisekoop, Nienke van Gent, Rogier de Boer, Anne Bregje Otto, Sigrid A Borleffs, Jan C. C Steingrover, Radjin Prins, Jan M Kuijpers, Taco W Wolfs, Tom F. W Geelen, Sibyl P. M Vulto, Irma Lansdorp, Peter Tesselaar, Kiki Borghans, Jose A. M Miedema, Frank |
| description | It remains uncertain whether full T cell reconstitution can be established in HIV-infected children and adults with long-term sustained virological control by highly active antiretroviral therapy (HAART). In this study, we comprehensively analyzed various phenotypical markers of CD4 T cell recovery. In addition to measuring T cell activation and proliferation markers, CD4 T cell generation and aging of the CD4 T cell compartment were assessed by measuring TCR excision circles and the fraction of CD31-expressing naive CD4 T cells. In all children and in adults with relatively high CD4 T cell counts at start of therapy (>200 cells/microl), total CD4 T cell numbers normalized within 1 year of therapy. After long-term HAART (4.4-9.6 years), naive CD4 T cell counts had normalized in both groups. Although in adults with low baseline CD4 T cell counts ( |
| doi_str_mv | 10.4049/jimmunol.181.2.1573 |
| format | Article |
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C ; Steingrover, Radjin ; Prins, Jan M ; Kuijpers, Taco W ; Wolfs, Tom F. W ; Geelen, Sibyl P. M ; Vulto, Irma ; Lansdorp, Peter ; Tesselaar, Kiki ; Borghans, Jose A. M ; Miedema, Frank</creator><creatorcontrib>Vrisekoop, Nienke ; van Gent, Rogier ; de Boer, Anne Bregje ; Otto, Sigrid A ; Borleffs, Jan C. C ; Steingrover, Radjin ; Prins, Jan M ; Kuijpers, Taco W ; Wolfs, Tom F. W ; Geelen, Sibyl P. M ; Vulto, Irma ; Lansdorp, Peter ; Tesselaar, Kiki ; Borghans, Jose A. M ; Miedema, Frank</creatorcontrib><description>It remains uncertain whether full T cell reconstitution can be established in HIV-infected children and adults with long-term sustained virological control by highly active antiretroviral therapy (HAART). In this study, we comprehensively analyzed various phenotypical markers of CD4 T cell recovery. In addition to measuring T cell activation and proliferation markers, CD4 T cell generation and aging of the CD4 T cell compartment were assessed by measuring TCR excision circles and the fraction of CD31-expressing naive CD4 T cells. In all children and in adults with relatively high CD4 T cell counts at start of therapy (>200 cells/microl), total CD4 T cell numbers normalized within 1 year of therapy. After long-term HAART (4.4-9.6 years), naive CD4 T cell counts had normalized in both groups. Although in adults with low baseline CD4 T cell counts (<200 cells/microl) total CD4 T cell numbers normalized eventually after at least 7 years of HAART, naive CD4 T cell counts had still not recovered. TCR excision circle data showed that thymic T cell production contributed to naive T cell recovery at all ages. The fraction of CD31-expressing naive CD4 T cells was found to be normal, suggesting that the CD4 T cell repertoire was diverse after long-term HAART. Hence, under sustained viral suppression during long-term HAART, the T cell compartment has the potential to fully recover by generating new naive T cells both in children and in adults with high baseline CD4 T cells counts. Irrespective of baseline CD4 T cell counts, reconstitution occurred without a significant effect on T cell aging as reflected by markers for replicative history.</description><identifier>ISSN: 0022-1767</identifier><identifier>EISSN: 1550-6606</identifier><identifier>DOI: 10.4049/jimmunol.181.2.1573</identifier><identifier>PMID: 18606713</identifier><language>eng</language><publisher>United States: Am Assoc Immnol</publisher><subject>Adolescent ; Adult ; Antiretroviral Therapy, Highly Active ; CD4 Lymphocyte Count ; CD4-Positive T-Lymphocytes - drug effects ; CD4-Positive T-Lymphocytes - immunology ; CD4-Positive T-Lymphocytes - virology ; Child ; Child, Preschool ; HIV Infections - drug therapy ; HIV Infections - immunology ; HIV Infections - virology ; HIV-1 ; Human immunodeficiency virus ; Humans ; Infant ; Ki-67 Antigen - immunology ; Ki-67 Antigen - metabolism ; Lymphocyte Activation ; Middle Aged ; Platelet Endothelial Cell Adhesion Molecule-1 - immunology ; Platelet Endothelial Cell Adhesion Molecule-1 - metabolism ; T-Lymphocyte Subsets - immunology</subject><ispartof>The Journal of immunology (1950), 2008-07, Vol.181 (2), p.1573-1581</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c411t-e8660d3cf0f5460278d7968a3f142c021c26677e609b38f99eb139ec681b39593</citedby><cites>FETCH-LOGICAL-c411t-e8660d3cf0f5460278d7968a3f142c021c26677e609b38f99eb139ec681b39593</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18606713$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Vrisekoop, Nienke</creatorcontrib><creatorcontrib>van Gent, Rogier</creatorcontrib><creatorcontrib>de Boer, Anne Bregje</creatorcontrib><creatorcontrib>Otto, Sigrid A</creatorcontrib><creatorcontrib>Borleffs, Jan C. C</creatorcontrib><creatorcontrib>Steingrover, Radjin</creatorcontrib><creatorcontrib>Prins, Jan M</creatorcontrib><creatorcontrib>Kuijpers, Taco W</creatorcontrib><creatorcontrib>Wolfs, Tom F. W</creatorcontrib><creatorcontrib>Geelen, Sibyl P. M</creatorcontrib><creatorcontrib>Vulto, Irma</creatorcontrib><creatorcontrib>Lansdorp, Peter</creatorcontrib><creatorcontrib>Tesselaar, Kiki</creatorcontrib><creatorcontrib>Borghans, Jose A. M</creatorcontrib><creatorcontrib>Miedema, Frank</creatorcontrib><title>Restoration of the CD4 T Cell Compartment after Long-Term Highly Active Antiretroviral Therapy without Phenotypical Signs of Accelerated Immunological Aging</title><title>The Journal of immunology (1950)</title><addtitle>J Immunol</addtitle><description>It remains uncertain whether full T cell reconstitution can be established in HIV-infected children and adults with long-term sustained virological control by highly active antiretroviral therapy (HAART). In this study, we comprehensively analyzed various phenotypical markers of CD4 T cell recovery. In addition to measuring T cell activation and proliferation markers, CD4 T cell generation and aging of the CD4 T cell compartment were assessed by measuring TCR excision circles and the fraction of CD31-expressing naive CD4 T cells. In all children and in adults with relatively high CD4 T cell counts at start of therapy (>200 cells/microl), total CD4 T cell numbers normalized within 1 year of therapy. After long-term HAART (4.4-9.6 years), naive CD4 T cell counts had normalized in both groups. Although in adults with low baseline CD4 T cell counts (<200 cells/microl) total CD4 T cell numbers normalized eventually after at least 7 years of HAART, naive CD4 T cell counts had still not recovered. TCR excision circle data showed that thymic T cell production contributed to naive T cell recovery at all ages. The fraction of CD31-expressing naive CD4 T cells was found to be normal, suggesting that the CD4 T cell repertoire was diverse after long-term HAART. Hence, under sustained viral suppression during long-term HAART, the T cell compartment has the potential to fully recover by generating new naive T cells both in children and in adults with high baseline CD4 T cells counts. Irrespective of baseline CD4 T cell counts, reconstitution occurred without a significant effect on T cell aging as reflected by markers for replicative history.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Antiretroviral Therapy, Highly Active</subject><subject>CD4 Lymphocyte Count</subject><subject>CD4-Positive T-Lymphocytes - drug effects</subject><subject>CD4-Positive T-Lymphocytes - immunology</subject><subject>CD4-Positive T-Lymphocytes - virology</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>HIV Infections - drug therapy</subject><subject>HIV Infections - immunology</subject><subject>HIV Infections - virology</subject><subject>HIV-1</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Infant</subject><subject>Ki-67 Antigen - immunology</subject><subject>Ki-67 Antigen - metabolism</subject><subject>Lymphocyte Activation</subject><subject>Middle Aged</subject><subject>Platelet Endothelial Cell Adhesion Molecule-1 - immunology</subject><subject>Platelet Endothelial Cell Adhesion Molecule-1 - metabolism</subject><subject>T-Lymphocyte Subsets - immunology</subject><issn>0022-1767</issn><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkcFu1DAURS1ERYfCFyAhr2CVwY4TJ1lGKbSVRqJqh7Xl8bwkrpw42E6j-Rc-th5mEOxYefHOu8_3XoQ-ULLOSFZ9edLDMI_WrGlJ1-ma5gV7hVY0z0nCOeGv0YqQNE1owYtL9Nb7J0IIJ2n2Bl3SMgIFZSv06wF8sE4GbUdsWxx6wM11hre4AWNwY4dJujDAGLBsAzi8sWOXbMEN-FZ3vTngWgX9DLgeg3YQnH3WThq87cHJ6YAXHXo7B3zfw2jDYdIqDh91N_rjtVopMBEMsMd3Jze2-43UnR67d-iilcbD-_N7hX58-7ptbpPN95u7pt4kKqM0JFBGv3umWtLmWXRYlPui4qVkLc1SRVKqUs6LAjipdqxsqwp2lFWgeEl3rMordoU-nXQnZ3_OMRAxaB9_ZuQIdvaCV4xQSsl_wZSUeR5PRZCdQOWs9w5aMTk9SHcQlIhje-JPeyK2J1JxbC9ufTzLz7sB9n93znVF4PMJ6GP2S8xb-EEaE3EqlmX5R-oFdLqnGw</recordid><startdate>20080715</startdate><enddate>20080715</enddate><creator>Vrisekoop, Nienke</creator><creator>van Gent, Rogier</creator><creator>de Boer, Anne Bregje</creator><creator>Otto, Sigrid A</creator><creator>Borleffs, Jan C. 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M</au><au>Vulto, Irma</au><au>Lansdorp, Peter</au><au>Tesselaar, Kiki</au><au>Borghans, Jose A. M</au><au>Miedema, Frank</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Restoration of the CD4 T Cell Compartment after Long-Term Highly Active Antiretroviral Therapy without Phenotypical Signs of Accelerated Immunological Aging</atitle><jtitle>The Journal of immunology (1950)</jtitle><addtitle>J Immunol</addtitle><date>2008-07-15</date><risdate>2008</risdate><volume>181</volume><issue>2</issue><spage>1573</spage><epage>1581</epage><pages>1573-1581</pages><issn>0022-1767</issn><eissn>1550-6606</eissn><abstract>It remains uncertain whether full T cell reconstitution can be established in HIV-infected children and adults with long-term sustained virological control by highly active antiretroviral therapy (HAART). In this study, we comprehensively analyzed various phenotypical markers of CD4 T cell recovery. In addition to measuring T cell activation and proliferation markers, CD4 T cell generation and aging of the CD4 T cell compartment were assessed by measuring TCR excision circles and the fraction of CD31-expressing naive CD4 T cells. In all children and in adults with relatively high CD4 T cell counts at start of therapy (>200 cells/microl), total CD4 T cell numbers normalized within 1 year of therapy. After long-term HAART (4.4-9.6 years), naive CD4 T cell counts had normalized in both groups. Although in adults with low baseline CD4 T cell counts (<200 cells/microl) total CD4 T cell numbers normalized eventually after at least 7 years of HAART, naive CD4 T cell counts had still not recovered. TCR excision circle data showed that thymic T cell production contributed to naive T cell recovery at all ages. The fraction of CD31-expressing naive CD4 T cells was found to be normal, suggesting that the CD4 T cell repertoire was diverse after long-term HAART. Hence, under sustained viral suppression during long-term HAART, the T cell compartment has the potential to fully recover by generating new naive T cells both in children and in adults with high baseline CD4 T cells counts. Irrespective of baseline CD4 T cell counts, reconstitution occurred without a significant effect on T cell aging as reflected by markers for replicative history.</abstract><cop>United States</cop><pub>Am Assoc Immnol</pub><pmid>18606713</pmid><doi>10.4049/jimmunol.181.2.1573</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Adolescent Adult Antiretroviral Therapy, Highly Active CD4 Lymphocyte Count CD4-Positive T-Lymphocytes - drug effects CD4-Positive T-Lymphocytes - immunology CD4-Positive T-Lymphocytes - virology Child Child, Preschool HIV Infections - drug therapy HIV Infections - immunology HIV Infections - virology HIV-1 Human immunodeficiency virus Humans Infant Ki-67 Antigen - immunology Ki-67 Antigen - metabolism Lymphocyte Activation Middle Aged Platelet Endothelial Cell Adhesion Molecule-1 - immunology Platelet Endothelial Cell Adhesion Molecule-1 - metabolism T-Lymphocyte Subsets - immunology |
| title | Restoration of the CD4 T Cell Compartment after Long-Term Highly Active Antiretroviral Therapy without Phenotypical Signs of Accelerated Immunological Aging |
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