Polyclonal Proliferation and Apoptosis of CCR5+ T Lymphocytes during Primary Human Immunodeficiency Virus Type 1 Infection: Regulation by Interleukin (IL)-2, IL-15, and Bcl-2
Identifieur interne : 00AE58 ( Main/Exploration ); précédent : 00AE57; suivant : 00AE59Polyclonal Proliferation and Apoptosis of CCR5+ T Lymphocytes during Primary Human Immunodeficiency Virus Type 1 Infection: Regulation by Interleukin (IL)-2, IL-15, and Bcl-2
Auteurs : John J. Zaunders ; Laure Moutouh-De Parseval ; Shinichi Kitada ; John C. Reed ; Steffney Rought [États-Unis] ; Davide Genini [États-Unis] ; Lorenzo Leoni [États-Unis] ; Anthony Kelleher [Australie] ; David A. Cooper [Australie] ; Don E. Smith [Australie] ; Pat Grey [Australie] ; Jérôme Estaquier [France] ; Susan Little [États-Unis] ; Douglas D. Richman [États-Unis] ; Jacques Corbeil [États-Unis]Source :
- The Journal of Infectious Diseases [ 0022-1899 ] ; 2003-06-01.
Descripteurs français
- Pascal (Inist)
- Wicri :
- topic : Homme.
English descriptors
- KwdEn :
Abstract
We measured apoptosis of subsets of T lymphocytes by single-cell analysis of caspase activation, to confirm high turnover of chemokine receptor CCR5+ T cells in subjects with acute, primary human immunodeficiency virus type 1 (HIV-1) infection (PHI). High levels of spontaneous apoptosis, consisting mainly of CD8+ T lymphocytes, were closely associated with increases in the activation markers Ki-67, CD38, and the HIV coreceptor CCR5 and with decreases in Bcl-2 and the interleukin (IL)-7 receptor at the single-cell level. Increased expression of Ki-67 and CCR5 ex vivo, as well as increased apoptosis, was seen in all T cell receptor β-chain variable region (TCRBV) subfamilies studied. The addition of IL-2 or IL-15, but not IL-7, significantly inhibited caspase activation, increased Bcl-2 expression, and rapidly initiated proliferation in vitro of CD8+ T cells expressing CCR5 and multiple TCRBV subfamilies. Furthermore, IL-15 receptor α-chain messenger RNA levels were increased in peripheral blood mononuclear cells during PHI. These results suggest that CCR5+Ki-67+Bcl-2dim activated T cells generated during PHI traffic via blood to tissue sites, where the cells may survive and/or further proliferate under the local influence of IL-2 or IL-15. Understanding cytokine effects on CCR5+ T cells will be important in understanding chronic HIV-1 replication and pathogenesis
Url:
DOI: 10.1086/375030
Affiliations:
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Le document en format XML
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>AIDS</term>
<term>Apoptosis</term>
<term>CCR5 chemokine receptor</term>
<term>Cell proliferation</term>
<term>HIV-1 virus</term>
<term>Human</term>
<term>Interleukin 15</term>
<term>Interleukin 2</term>
<term>Regulation</term>
<term>T-Lymphocyte</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Apoptose</term>
<term>Homme</term>
<term>Interleukine 15</term>
<term>Interleukine 2</term>
<term>Lymphocyte T</term>
<term>Multiplication cellulaire</term>
<term>Protéine Bcl2</term>
<term>Récepteur chimiokine CCR5</term>
<term>Réglementation</term>
<term>SIDA</term>
<term>Virus HIV1</term>
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<front><div type="abstract">We measured apoptosis of subsets of T lymphocytes by single-cell analysis of caspase activation, to confirm high turnover of chemokine receptor CCR5+ T cells in subjects with acute, primary human immunodeficiency virus type 1 (HIV-1) infection (PHI). High levels of spontaneous apoptosis, consisting mainly of CD8+ T lymphocytes, were closely associated with increases in the activation markers Ki-67, CD38, and the HIV coreceptor CCR5 and with decreases in Bcl-2 and the interleukin (IL)-7 receptor at the single-cell level. Increased expression of Ki-67 and CCR5 ex vivo, as well as increased apoptosis, was seen in all T cell receptor β-chain variable region (TCRBV) subfamilies studied. The addition of IL-2 or IL-15, but not IL-7, significantly inhibited caspase activation, increased Bcl-2 expression, and rapidly initiated proliferation in vitro of CD8+ T cells expressing CCR5 and multiple TCRBV subfamilies. Furthermore, IL-15 receptor α-chain messenger RNA levels were increased in peripheral blood mononuclear cells during PHI. These results suggest that CCR5+Ki-67+Bcl-2dim activated T cells generated during PHI traffic via blood to tissue sites, where the cells may survive and/or further proliferate under the local influence of IL-2 or IL-15. Understanding cytokine effects on CCR5+ T cells will be important in understanding chronic HIV-1 replication and pathogenesis</div>
</front>
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<name sortKey="Smith, Don E" sort="Smith, Don E" uniqKey="Smith D" first="Don E." last="Smith">Don E. Smith</name>
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<country name="France"><region name="Île-de-France"><name sortKey="Estaquier, Jerome" sort="Estaquier, Jerome" uniqKey="Estaquier J" first="Jérôme" last="Estaquier">Jérôme Estaquier</name>
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