Cargando…
Measuring Recent Thymic Emigrants in Blood of Normal and HIV-1–Infected Individuals before and after Effective Therapy
The role of the thymus in HIV-1 pathogenesis remains unclear. We developed an assay to quantify the number of recent thymic emigrants in blood based on the detection of a major excisional DNA byproduct (termed α1 circle) of T cell receptor rearrangement. By studying 532 normal individuals, we found...
Autores principales: | , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
1999
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2195623/ https://www.ncbi.nlm.nih.gov/pubmed/10477556 |
_version_ | 1782147888589045760 |
---|---|
author | Zhang, Linqi Lewin, Sharon R. Markowitz, Martin Lin, Hsi-Hsun Skulsky, Eva Karanicolas, Rose He, Yuxian Jin, Xia Tuttleton, Sarah Vesanen, Mika Spiegel, Hans Kost, Rhonda van Lunzen, Jan Stellbrink, Hans-Juergen Wolinsky, Steven Borkowsky, William Palumbo, Paul Kostrikis, Leondios G. Ho, David D. |
author_facet | Zhang, Linqi Lewin, Sharon R. Markowitz, Martin Lin, Hsi-Hsun Skulsky, Eva Karanicolas, Rose He, Yuxian Jin, Xia Tuttleton, Sarah Vesanen, Mika Spiegel, Hans Kost, Rhonda van Lunzen, Jan Stellbrink, Hans-Juergen Wolinsky, Steven Borkowsky, William Palumbo, Paul Kostrikis, Leondios G. Ho, David D. |
author_sort | Zhang, Linqi |
collection | PubMed |
description | The role of the thymus in HIV-1 pathogenesis remains unclear. We developed an assay to quantify the number of recent thymic emigrants in blood based on the detection of a major excisional DNA byproduct (termed α1 circle) of T cell receptor rearrangement. By studying 532 normal individuals, we found that α1 circle numbers in blood remain high for the first 10–15 yr of life, a sharp drop is seen in the late teen years, and a gradual decline occurs thereafter. Compared with age-matched uninfected control individuals, α1 circle numbers in HIV-1–infected adults were significantly reduced; however, there were many individuals with normal α1 circle numbers. In 74 individuals receiving highly active antiretroviral therapy, we found no appreciable effect on α1 circle numbers in those whose baseline values were already within the normal range, but significant increases were observed in those with a preexisting impairment. The increases in α1 circle numbers were, however, numerically insufficient to account for the rise in levels of naive T lymphocytes. Overall, it is difficult to invoke thymic regenerative failure as a generalized mechanism for CD4 lymphocyte depletion in HIV-1 infection, as α1 circle numbers are normal in a substantial subset of HIV-1–infected individuals. |
format | Text |
id | pubmed-2195623 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 1999 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21956232008-04-16 Measuring Recent Thymic Emigrants in Blood of Normal and HIV-1–Infected Individuals before and after Effective Therapy Zhang, Linqi Lewin, Sharon R. Markowitz, Martin Lin, Hsi-Hsun Skulsky, Eva Karanicolas, Rose He, Yuxian Jin, Xia Tuttleton, Sarah Vesanen, Mika Spiegel, Hans Kost, Rhonda van Lunzen, Jan Stellbrink, Hans-Juergen Wolinsky, Steven Borkowsky, William Palumbo, Paul Kostrikis, Leondios G. Ho, David D. J Exp Med Original Article The role of the thymus in HIV-1 pathogenesis remains unclear. We developed an assay to quantify the number of recent thymic emigrants in blood based on the detection of a major excisional DNA byproduct (termed α1 circle) of T cell receptor rearrangement. By studying 532 normal individuals, we found that α1 circle numbers in blood remain high for the first 10–15 yr of life, a sharp drop is seen in the late teen years, and a gradual decline occurs thereafter. Compared with age-matched uninfected control individuals, α1 circle numbers in HIV-1–infected adults were significantly reduced; however, there were many individuals with normal α1 circle numbers. In 74 individuals receiving highly active antiretroviral therapy, we found no appreciable effect on α1 circle numbers in those whose baseline values were already within the normal range, but significant increases were observed in those with a preexisting impairment. The increases in α1 circle numbers were, however, numerically insufficient to account for the rise in levels of naive T lymphocytes. Overall, it is difficult to invoke thymic regenerative failure as a generalized mechanism for CD4 lymphocyte depletion in HIV-1 infection, as α1 circle numbers are normal in a substantial subset of HIV-1–infected individuals. The Rockefeller University Press 1999-09-06 /pmc/articles/PMC2195623/ /pubmed/10477556 Text en © 1999 The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Original Article Zhang, Linqi Lewin, Sharon R. Markowitz, Martin Lin, Hsi-Hsun Skulsky, Eva Karanicolas, Rose He, Yuxian Jin, Xia Tuttleton, Sarah Vesanen, Mika Spiegel, Hans Kost, Rhonda van Lunzen, Jan Stellbrink, Hans-Juergen Wolinsky, Steven Borkowsky, William Palumbo, Paul Kostrikis, Leondios G. Ho, David D. Measuring Recent Thymic Emigrants in Blood of Normal and HIV-1–Infected Individuals before and after Effective Therapy |
title | Measuring Recent Thymic Emigrants in Blood of Normal and HIV-1–Infected Individuals before and after Effective Therapy |
title_full | Measuring Recent Thymic Emigrants in Blood of Normal and HIV-1–Infected Individuals before and after Effective Therapy |
title_fullStr | Measuring Recent Thymic Emigrants in Blood of Normal and HIV-1–Infected Individuals before and after Effective Therapy |
title_full_unstemmed | Measuring Recent Thymic Emigrants in Blood of Normal and HIV-1–Infected Individuals before and after Effective Therapy |
title_short | Measuring Recent Thymic Emigrants in Blood of Normal and HIV-1–Infected Individuals before and after Effective Therapy |
title_sort | measuring recent thymic emigrants in blood of normal and hiv-1–infected individuals before and after effective therapy |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2195623/ https://www.ncbi.nlm.nih.gov/pubmed/10477556 |
work_keys_str_mv | AT zhanglinqi measuringrecentthymicemigrantsinbloodofnormalandhiv1infectedindividualsbeforeandaftereffectivetherapy AT lewinsharonr measuringrecentthymicemigrantsinbloodofnormalandhiv1infectedindividualsbeforeandaftereffectivetherapy AT markowitzmartin measuringrecentthymicemigrantsinbloodofnormalandhiv1infectedindividualsbeforeandaftereffectivetherapy AT linhsihsun measuringrecentthymicemigrantsinbloodofnormalandhiv1infectedindividualsbeforeandaftereffectivetherapy AT skulskyeva measuringrecentthymicemigrantsinbloodofnormalandhiv1infectedindividualsbeforeandaftereffectivetherapy AT karanicolasrose measuringrecentthymicemigrantsinbloodofnormalandhiv1infectedindividualsbeforeandaftereffectivetherapy AT heyuxian measuringrecentthymicemigrantsinbloodofnormalandhiv1infectedindividualsbeforeandaftereffectivetherapy AT jinxia measuringrecentthymicemigrantsinbloodofnormalandhiv1infectedindividualsbeforeandaftereffectivetherapy AT tuttletonsarah measuringrecentthymicemigrantsinbloodofnormalandhiv1infectedindividualsbeforeandaftereffectivetherapy AT vesanenmika measuringrecentthymicemigrantsinbloodofnormalandhiv1infectedindividualsbeforeandaftereffectivetherapy AT spiegelhans measuringrecentthymicemigrantsinbloodofnormalandhiv1infectedindividualsbeforeandaftereffectivetherapy AT kostrhonda measuringrecentthymicemigrantsinbloodofnormalandhiv1infectedindividualsbeforeandaftereffectivetherapy AT vanlunzenjan measuringrecentthymicemigrantsinbloodofnormalandhiv1infectedindividualsbeforeandaftereffectivetherapy AT stellbrinkhansjuergen measuringrecentthymicemigrantsinbloodofnormalandhiv1infectedindividualsbeforeandaftereffectivetherapy AT wolinskysteven measuringrecentthymicemigrantsinbloodofnormalandhiv1infectedindividualsbeforeandaftereffectivetherapy AT borkowskywilliam measuringrecentthymicemigrantsinbloodofnormalandhiv1infectedindividualsbeforeandaftereffectivetherapy AT palumbopaul measuringrecentthymicemigrantsinbloodofnormalandhiv1infectedindividualsbeforeandaftereffectivetherapy AT kostrikisleondiosg measuringrecentthymicemigrantsinbloodofnormalandhiv1infectedindividualsbeforeandaftereffectivetherapy AT hodavidd measuringrecentthymicemigrantsinbloodofnormalandhiv1infectedindividualsbeforeandaftereffectivetherapy |