Poor immune reconstitution in HIV-infected patients associates with high percentage of regulatory CD4+ T Cells
Autor(a) principal: | |
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Data de Publicação: | 2013 |
Outros Autores: | , , , , , , , , |
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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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 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
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 instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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1777303665708630016 |