Evidence for Increased T Cell Turnover and Decreased Thymic Output in HIV Infection
The effects of HIV infection upon the thymus and peripheral T cell turnover have been implicated in the pathogenesis of AIDS. In this study, we investigated whether decreased thymic output, increased T cell proliferation, or both can occur in HIV infection. We measured peripheral blood levels of TCR...
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| Veröffentlicht in: | The Journal of immunology (1950) 2001-12, Vol.167 (11), p.6663-6668 |
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| container_title | The Journal of immunology (1950) |
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| creator | Douek, Daniel C Betts, Michael R Hill, Brenna J Little, Susan J Lempicki, Richard Metcalf, Julia A Casazza, Joseph Yoder, Christian Adelsberger, Joseph W Stevens, Randy A Baseler, Michael W Keiser, Philip Richman, Douglas D Davey, Richard T Koup, Richard A |
| description | The effects of HIV infection upon the thymus and peripheral T cell turnover have been implicated in the pathogenesis of AIDS. In this study, we investigated whether decreased thymic output, increased T cell proliferation, or both can occur in HIV infection. We measured peripheral blood levels of TCR rearrangement excision circles (TREC) and parameters of cell proliferation, including Ki67 expression and ex vivo bromodeoxyuridine incorporation in 22 individuals with early untreated HIV disease and in 15 HIV-infected individuals undergoing temporary interruption of therapy. We found an inverse association between increased T cell proliferation with rapid viral recrudescence and a decrease in TREC levels. However, during early HIV infection, we found that CD45RO-CD27high (naive) CD4+ T cell proliferation did not increase, despite a loss of TREC within naive CD4+ T cells. A possible explanation for this is that decreased thymic output occurs in HIV-infected humans. This suggests that the loss of TREC during HIV infection can arise from a combination of increased T cell proliferation and decreased thymic output, and that both mechanisms can contribute to the perturbations in T cell homeostasis that underlie the pathogenesis of AIDS. |
| doi_str_mv | 10.4049/jimmunol.167.11.6663 |
| format | Article |
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In this study, we investigated whether decreased thymic output, increased T cell proliferation, or both can occur in HIV infection. We measured peripheral blood levels of TCR rearrangement excision circles (TREC) and parameters of cell proliferation, including Ki67 expression and ex vivo bromodeoxyuridine incorporation in 22 individuals with early untreated HIV disease and in 15 HIV-infected individuals undergoing temporary interruption of therapy. We found an inverse association between increased T cell proliferation with rapid viral recrudescence and a decrease in TREC levels. However, during early HIV infection, we found that CD45RO-CD27high (naive) CD4+ T cell proliferation did not increase, despite a loss of TREC within naive CD4+ T cells. A possible explanation for this is that decreased thymic output occurs in HIV-infected humans. 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Betts, Michael R ; Hill, Brenna J ; Little, Susan J ; Lempicki, Richard ; Metcalf, Julia A ; Casazza, Joseph ; Yoder, Christian ; Adelsberger, Joseph W ; Stevens, Randy A ; Baseler, Michael W ; Keiser, Philip ; Richman, Douglas D ; Davey, Richard T ; Koup, Richard A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c367t-f4c718a48bb8fcffa792ab6ec72f2c3f6d0c3b8505f3f1159d91bacedb4284533</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Antiretroviral Therapy, Highly Active</topic><topic>Bromodeoxyuridine - metabolism</topic><topic>CD4-Positive T-Lymphocytes - immunology</topic><topic>CD4-Positive T-Lymphocytes - pathology</topic><topic>Gene Rearrangement, T-Lymphocyte</topic><topic>HIV Infections - drug therapy</topic><topic>HIV Infections - immunology</topic><topic>HIV Infections - pathology</topic><topic>Human immunodeficiency virus</topic><topic>Humans</topic><topic>Immunologic Memory</topic><topic>Interphase - immunology</topic><topic>Ki-67 Antigen - biosynthesis</topic><topic>Lymphocyte Activation</topic><topic>Middle Aged</topic><topic>T-Lymphocyte Subsets - immunology</topic><topic>T-Lymphocyte Subsets - metabolism</topic><topic>T-Lymphocyte Subsets - pathology</topic><topic>Thymus Gland - immunology</topic><topic>Thymus Gland - metabolism</topic><topic>Thymus Gland - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Douek, Daniel C</creatorcontrib><creatorcontrib>Betts, Michael R</creatorcontrib><creatorcontrib>Hill, Brenna J</creatorcontrib><creatorcontrib>Little, Susan J</creatorcontrib><creatorcontrib>Lempicki, Richard</creatorcontrib><creatorcontrib>Metcalf, Julia A</creatorcontrib><creatorcontrib>Casazza, Joseph</creatorcontrib><creatorcontrib>Yoder, Christian</creatorcontrib><creatorcontrib>Adelsberger, Joseph W</creatorcontrib><creatorcontrib>Stevens, Randy A</creatorcontrib><creatorcontrib>Baseler, Michael W</creatorcontrib><creatorcontrib>Keiser, Philip</creatorcontrib><creatorcontrib>Richman, Douglas D</creatorcontrib><creatorcontrib>Davey, Richard T</creatorcontrib><creatorcontrib>Koup, Richard A</creatorcontrib><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>MEDLINE - Academic</collection><jtitle>The Journal of immunology (1950)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Douek, Daniel C</au><au>Betts, Michael R</au><au>Hill, Brenna J</au><au>Little, Susan J</au><au>Lempicki, Richard</au><au>Metcalf, Julia A</au><au>Casazza, Joseph</au><au>Yoder, Christian</au><au>Adelsberger, Joseph W</au><au>Stevens, Randy A</au><au>Baseler, Michael W</au><au>Keiser, Philip</au><au>Richman, Douglas D</au><au>Davey, Richard T</au><au>Koup, Richard A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Evidence for Increased T Cell Turnover and Decreased Thymic Output in HIV Infection</atitle><jtitle>The Journal of immunology (1950)</jtitle><addtitle>J Immunol</addtitle><date>2001-12-01</date><risdate>2001</risdate><volume>167</volume><issue>11</issue><spage>6663</spage><epage>6668</epage><pages>6663-6668</pages><issn>0022-1767</issn><eissn>1550-6606</eissn><abstract>The effects of HIV infection upon the thymus and peripheral T cell turnover have been implicated in the pathogenesis of AIDS. In this study, we investigated whether decreased thymic output, increased T cell proliferation, or both can occur in HIV infection. We measured peripheral blood levels of TCR rearrangement excision circles (TREC) and parameters of cell proliferation, including Ki67 expression and ex vivo bromodeoxyuridine incorporation in 22 individuals with early untreated HIV disease and in 15 HIV-infected individuals undergoing temporary interruption of therapy. We found an inverse association between increased T cell proliferation with rapid viral recrudescence and a decrease in TREC levels. However, during early HIV infection, we found that CD45RO-CD27high (naive) CD4+ T cell proliferation did not increase, despite a loss of TREC within naive CD4+ T cells. A possible explanation for this is that decreased thymic output occurs in HIV-infected humans. This suggests that the loss of TREC during HIV infection can arise from a combination of increased T cell proliferation and decreased thymic output, and that both mechanisms can contribute to the perturbations in T cell homeostasis that underlie the pathogenesis of AIDS.</abstract><cop>United States</cop><pub>Am Assoc Immnol</pub><pmid>11714838</pmid><doi>10.4049/jimmunol.167.11.6663</doi><tpages>6</tpages></addata></record> |
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| subjects | Adult Aged Aged, 80 and over Antiretroviral Therapy, Highly Active Bromodeoxyuridine - metabolism CD4-Positive T-Lymphocytes - immunology CD4-Positive T-Lymphocytes - pathology Gene Rearrangement, T-Lymphocyte HIV Infections - drug therapy HIV Infections - immunology HIV Infections - pathology Human immunodeficiency virus Humans Immunologic Memory Interphase - immunology Ki-67 Antigen - biosynthesis Lymphocyte Activation Middle Aged T-Lymphocyte Subsets - immunology T-Lymphocyte Subsets - metabolism T-Lymphocyte Subsets - pathology Thymus Gland - immunology Thymus Gland - metabolism Thymus Gland - pathology |
| title | Evidence for Increased T Cell Turnover and Decreased Thymic Output in HIV Infection |
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