Poor immune reconstitution in HIV-infected patients associates with high percentage of regulatory CD4+ T Cells

Detalhes bibliográficos
Autor(a) principal: Horta, Ana
Data de Publicação: 2013
Outros Autores: Nóbrega, Cláudia, Machado, Pedro Amorim, Teixeira, Vítor Emanuel Coutinho, Silva, Palmira Conceição Araújo Barreira, Boavida, Susana, Costa, Patrício Soares, Castro, Rui Sarmento, Castro, António G., Neves, Margarida Correia
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/1822/25582
Resumo: CD4(+) regulatory T cells (Tregs) are essential for the maintenance of the immune system's equilibrium, by dampening the activation of potential auto-reactive T cells and avoiding excessive immune activation. To correctly perform their function, Tregs must be maintained at the right proportion with respect to effector T cells. Since this equilibrium is frequently disrupted in individuals infected with the human immunodeficiency virus (HIV), we hypothesize that its deregulation could hamper immune reconstitution in patients with poor CD4(+) T cell recovery under highly active antiretroviral therapy (HAART). We analysed Tregs percentages amongst CD4(+) T cells in 53 HIV-infected patients under HAART, with suppression of viral replication and distinct levels of immune reconstitution. As controls, 51 healthy individuals were also analysed. We observed that amongst the patients with Nadir values (the lowest CD4(+) T cell counts achieved) <200 cells/mu L, the individuals with high Tregs percentages (>= 10% of total CD4(+) T cells) had the worse CD4(+) T cell reconstitution. In accordance, the well-described direct correlation between the Nadir value and CD4(+) T cell reconstitution is clearly more evident in individuals with high Tregs proportions. Furthermore, we observed a strong negative correlation between Tregs percentages and CD4(+) T cell recovery among immunological non-responder HIV+ individuals. All together, this work shows that high Tregs frequency is an important factor associated with sub-optimal CD4(+) T cell recovery. This is particularly relevant for immunological non-responders with low Nadir values. Our results suggest that the Tregs proportion might be of clinical relevance to define cut-offs for HAART initiation.
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spelling Poor immune reconstitution in HIV-infected patients associates with high percentage of regulatory CD4+ T CellsScience & TechnologyCD4(+) regulatory T cells (Tregs) are essential for the maintenance of the immune system's equilibrium, by dampening the activation of potential auto-reactive T cells and avoiding excessive immune activation. To correctly perform their function, Tregs must be maintained at the right proportion with respect to effector T cells. Since this equilibrium is frequently disrupted in individuals infected with the human immunodeficiency virus (HIV), we hypothesize that its deregulation could hamper immune reconstitution in patients with poor CD4(+) T cell recovery under highly active antiretroviral therapy (HAART). We analysed Tregs percentages amongst CD4(+) T cells in 53 HIV-infected patients under HAART, with suppression of viral replication and distinct levels of immune reconstitution. As controls, 51 healthy individuals were also analysed. We observed that amongst the patients with Nadir values (the lowest CD4(+) T cell counts achieved) <200 cells/mu L, the individuals with high Tregs percentages (>= 10% of total CD4(+) T cells) had the worse CD4(+) T cell reconstitution. In accordance, the well-described direct correlation between the Nadir value and CD4(+) T cell reconstitution is clearly more evident in individuals with high Tregs proportions. Furthermore, we observed a strong negative correlation between Tregs percentages and CD4(+) T cell recovery among immunological non-responder HIV+ individuals. All together, this work shows that high Tregs frequency is an important factor associated with sub-optimal CD4(+) T cell recovery. This is particularly relevant for immunological non-responders with low Nadir values. Our results suggest that the Tregs proportion might be of clinical relevance to define cut-offs for HAART initiation.This work was supported by the Portuguese Foundation for Science and Technology (FCT; PIC/IC/83313/2007; http://www.fct.pt/apoios/projectos/consulta/vglobal_projecto.phtml.en?idProjecto = 83313&idElemConcurso = 1689). CN and PB-S received a fellowship from FCT (SFRH/BPD/65380/2009 and SFRH/BD/73544/2010, respectively). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.PLOSUniversidade do MinhoHorta, AnaNóbrega, CláudiaMachado, Pedro AmorimTeixeira, Vítor Emanuel CoutinhoSilva, Palmira Conceição Araújo BarreiraBoavida, SusanaCosta, Patrício SoaresCastro, Rui SarmentoCastro, António G.Neves, Margarida Correia2013-082013-08-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/25582eng1932-620310.1371/journal.pone.005733623437372http://dx.plos.org/10.1371/journal.pone.0057336info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:01:41ZPortal AgregadorONG
dc.title.none.fl_str_mv Poor immune reconstitution in HIV-infected patients associates with high percentage of regulatory CD4+ T Cells
title Poor immune reconstitution in HIV-infected patients associates with high percentage of regulatory CD4+ T Cells
spellingShingle Poor immune reconstitution in HIV-infected patients associates with high percentage of regulatory CD4+ T Cells
Horta, Ana
Science & Technology
title_short Poor immune reconstitution in HIV-infected patients associates with high percentage of regulatory CD4+ T Cells
title_full Poor immune reconstitution in HIV-infected patients associates with high percentage of regulatory CD4+ T Cells
title_fullStr Poor immune reconstitution in HIV-infected patients associates with high percentage of regulatory CD4+ T Cells
title_full_unstemmed Poor immune reconstitution in HIV-infected patients associates with high percentage of regulatory CD4+ T Cells
title_sort Poor immune reconstitution in HIV-infected patients associates with high percentage of regulatory CD4+ T Cells
author Horta, Ana
author_facet Horta, Ana
Nóbrega, Cláudia
Machado, Pedro Amorim
Teixeira, Vítor Emanuel Coutinho
Silva, Palmira Conceição Araújo Barreira
Boavida, Susana
Costa, Patrício Soares
Castro, Rui Sarmento
Castro, António G.
Neves, Margarida Correia
author_role author
author2 Nóbrega, Cláudia
Machado, Pedro Amorim
Teixeira, Vítor Emanuel Coutinho
Silva, Palmira Conceição Araújo Barreira
Boavida, Susana
Costa, Patrício Soares
Castro, Rui Sarmento
Castro, António G.
Neves, Margarida Correia
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade do Minho
dc.contributor.author.fl_str_mv Horta, Ana
Nóbrega, Cláudia
Machado, Pedro Amorim
Teixeira, Vítor Emanuel Coutinho
Silva, Palmira Conceição Araújo Barreira
Boavida, Susana
Costa, Patrício Soares
Castro, Rui Sarmento
Castro, António G.
Neves, Margarida Correia
dc.subject.por.fl_str_mv Science & Technology
topic Science & Technology
description CD4(+) regulatory T cells (Tregs) are essential for the maintenance of the immune system's equilibrium, by dampening the activation of potential auto-reactive T cells and avoiding excessive immune activation. To correctly perform their function, Tregs must be maintained at the right proportion with respect to effector T cells. Since this equilibrium is frequently disrupted in individuals infected with the human immunodeficiency virus (HIV), we hypothesize that its deregulation could hamper immune reconstitution in patients with poor CD4(+) T cell recovery under highly active antiretroviral therapy (HAART). We analysed Tregs percentages amongst CD4(+) T cells in 53 HIV-infected patients under HAART, with suppression of viral replication and distinct levels of immune reconstitution. As controls, 51 healthy individuals were also analysed. We observed that amongst the patients with Nadir values (the lowest CD4(+) T cell counts achieved) <200 cells/mu L, the individuals with high Tregs percentages (>= 10% of total CD4(+) T cells) had the worse CD4(+) T cell reconstitution. In accordance, the well-described direct correlation between the Nadir value and CD4(+) T cell reconstitution is clearly more evident in individuals with high Tregs proportions. Furthermore, we observed a strong negative correlation between Tregs percentages and CD4(+) T cell recovery among immunological non-responder HIV+ individuals. All together, this work shows that high Tregs frequency is an important factor associated with sub-optimal CD4(+) T cell recovery. This is particularly relevant for immunological non-responders with low Nadir values. Our results suggest that the Tregs proportion might be of clinical relevance to define cut-offs for HAART initiation.
publishDate 2013
dc.date.none.fl_str_mv 2013-08
2013-08-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/1822/25582
url http://hdl.handle.net/1822/25582
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 1932-6203
10.1371/journal.pone.0057336
23437372
http://dx.plos.org/10.1371/journal.pone.0057336
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eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv PLOS
publisher.none.fl_str_mv PLOS
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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