Unveiling altered CD8 T-cell metabolism and homeostatic proliferation behind a low CD4/CD8 ratio in ART-suppressed HIV individuals with normal CD4 recovery

[Background:] People living with chronic HIV (PLWH) show immune dysfunction, despite viral suppression and normal CD4 recovery, particularly those with low CD4/CD8 ratios. Subjacent cellular alterations of such a reliable marker of clinical progression remain elusive.

Detalles Bibliográficos
Autores: Garrido-Rodríguez, Vanesa, Bulnes-Ramos, Ángel, Olivas-Martínez, Israel, Pozo-Balado, María Del Mar, Tejerina-Picado, Francisco, Gutiérrez, Félix, Marco-Sánchez, Cristina, Tiraboschi, Juan Manuel, Castillo-Navarro, Antonia, Bernal, Enrique, García-Guerrero, María Carmen, Puertas, María Carmen, Peraire, Joaquim, Rull, Anna, Martinez-Picado, Javier, Pacheco, Yolanda M.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/407739
Acceso en línea:http://hdl.handle.net/10261/407739
https://api.elsevier.com/content/abstract/scopus_id/105017101609
Access Level:acceso abierto
Palabra clave:CD4/CD8 ratio
HIV-infection
Immunometabolism
Nadir-CD4 T cell
Thymic output
Viral reservoir
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dc.title.none.fl_str_mv Unveiling altered CD8 T-cell metabolism and homeostatic proliferation behind a low CD4/CD8 ratio in ART-suppressed HIV individuals with normal CD4 recovery
title Unveiling altered CD8 T-cell metabolism and homeostatic proliferation behind a low CD4/CD8 ratio in ART-suppressed HIV individuals with normal CD4 recovery
spellingShingle Unveiling altered CD8 T-cell metabolism and homeostatic proliferation behind a low CD4/CD8 ratio in ART-suppressed HIV individuals with normal CD4 recovery
Garrido-Rodríguez, Vanesa
CD4/CD8 ratio
HIV-infection
Immunometabolism
Nadir-CD4 T cell
Thymic output
Viral reservoir
title_short Unveiling altered CD8 T-cell metabolism and homeostatic proliferation behind a low CD4/CD8 ratio in ART-suppressed HIV individuals with normal CD4 recovery
title_full Unveiling altered CD8 T-cell metabolism and homeostatic proliferation behind a low CD4/CD8 ratio in ART-suppressed HIV individuals with normal CD4 recovery
title_fullStr Unveiling altered CD8 T-cell metabolism and homeostatic proliferation behind a low CD4/CD8 ratio in ART-suppressed HIV individuals with normal CD4 recovery
title_full_unstemmed Unveiling altered CD8 T-cell metabolism and homeostatic proliferation behind a low CD4/CD8 ratio in ART-suppressed HIV individuals with normal CD4 recovery
title_sort Unveiling altered CD8 T-cell metabolism and homeostatic proliferation behind a low CD4/CD8 ratio in ART-suppressed HIV individuals with normal CD4 recovery
dc.creator.none.fl_str_mv Garrido-Rodríguez, Vanesa
Bulnes-Ramos, Ángel
Olivas-Martínez, Israel
Pozo-Balado, María Del Mar
Tejerina-Picado, Francisco
Gutiérrez, Félix
Marco-Sánchez, Cristina
Tiraboschi, Juan Manuel
Castillo-Navarro, Antonia
Bernal, Enrique
García-Guerrero, María Carmen
Puertas, María Carmen
Peraire, Joaquim
Rull, Anna
Martinez-Picado, Javier
Pacheco, Yolanda M.
author Garrido-Rodríguez, Vanesa
author_facet Garrido-Rodríguez, Vanesa
Bulnes-Ramos, Ángel
Olivas-Martínez, Israel
Pozo-Balado, María Del Mar
Tejerina-Picado, Francisco
Gutiérrez, Félix
Marco-Sánchez, Cristina
Tiraboschi, Juan Manuel
Castillo-Navarro, Antonia
Bernal, Enrique
García-Guerrero, María Carmen
Puertas, María Carmen
Peraire, Joaquim
Rull, Anna
Martinez-Picado, Javier
Pacheco, Yolanda M.
author_role author
author2 Bulnes-Ramos, Ángel
Olivas-Martínez, Israel
Pozo-Balado, María Del Mar
Tejerina-Picado, Francisco
Gutiérrez, Félix
Marco-Sánchez, Cristina
Tiraboschi, Juan Manuel
Castillo-Navarro, Antonia
Bernal, Enrique
García-Guerrero, María Carmen
Puertas, María Carmen
Peraire, Joaquim
Rull, Anna
Martinez-Picado, Javier
Pacheco, Yolanda M.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv European Commission
Agencia Estatal de Investigación (España)
Ministerio de Ciencia, Innovación y Universidades (España)
Instituto de Salud Carlos III
Junta de Andalucía
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv CD4/CD8 ratio
HIV-infection
Immunometabolism
Nadir-CD4 T cell
Thymic output
Viral reservoir
topic CD4/CD8 ratio
HIV-infection
Immunometabolism
Nadir-CD4 T cell
Thymic output
Viral reservoir
description [Background:] People living with chronic HIV (PLWH) show immune dysfunction, despite viral suppression and normal CD4 recovery, particularly those with low CD4/CD8 ratios. Subjacent cellular alterations of such a reliable marker of clinical progression remain elusive.
publishDate 2025
dc.date.none.fl_str_mv 2025
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/407739
https://api.elsevier.com/content/abstract/scopus_id/105017101609
url http://hdl.handle.net/10261/407739
https://api.elsevier.com/content/abstract/scopus_id/105017101609
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
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info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016 (ISCIII)/PI18%2F01216
info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI20%2F00326
info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI21%2F00357
info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI19%2F00298
The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI https://doi.org/10.3389/fimmu.2025.1617674
https://doi.org/10.3389/fimmu.2025.1617674
Sí
dc.rights.none.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 Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
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spelling Unveiling altered CD8 T-cell metabolism and homeostatic proliferation behind a low CD4/CD8 ratio in ART-suppressed HIV individuals with normal CD4 recoveryGarrido-Rodríguez, VanesaBulnes-Ramos, ÁngelOlivas-Martínez, IsraelPozo-Balado, María Del MarTejerina-Picado, FranciscoGutiérrez, FélixMarco-Sánchez, CristinaTiraboschi, Juan ManuelCastillo-Navarro, AntoniaBernal, EnriqueGarcía-Guerrero, María CarmenPuertas, María CarmenPeraire, JoaquimRull, AnnaMartinez-Picado, JavierPacheco, Yolanda M.CD4/CD8 ratioHIV-infectionImmunometabolismNadir-CD4 T cellThymic outputViral reservoir[Background:] People living with chronic HIV (PLWH) show immune dysfunction, despite viral suppression and normal CD4 recovery, particularly those with low CD4/CD8 ratios. Subjacent cellular alterations of such a reliable marker of clinical progression remain elusive.[Methods:] Categorization by CD4/CD8 ratio after three year of therapy (R < 0.8/R > 1.2, n = 28/n = 24) and post-hoc reclassification by nadir-CD4 (N ≤ 350/N > 350) were performed in PLWH achieving viral suppression and CD4 ≥ 500. CD4 T cell–associated viral reservoir, as well as metabolism-related gene expression, glucose uptake ability, relative telomere length (RTL), and thymic output for CD4 and CD8 T cells, were determined.[Results:] Patients with a CD4/CD8 ratio < 0.8 exhibited reduced CD8 T-cell glucose uptake ability after stimulation (p = 0.007) and trends to shorter RTL (p = 0.093) and to larger CD4-associated viral reservoir (p = 0.068) than R > 1.2. Differently, patients with nadir ≤350 exhibited altered CD4 and CD8 T-cell expression of metabolism-related genes, although no differences in glucose uptake ability, and shorter RTL in both cell subsets, but similar viral reservoir to patients with nadir >350. Remarkably, viral reservoir and both CD4 and CD8 thymic output showed inverse associations (r = −0.623, p = 0.01 and r = −0.661, p = 0.038, respectively).[Conclusion:] A low CD4/CD8 ratio in chronic PLWH stands on a larger viral reservoir in CD4 T cells and metabolic alterations in CD8 T cells, probably related to its exhaustion and compromised effector functionality, and thymic output could contribute to such alterations. Patients with lower nadir-CD4 showed a resting-like CD4 phenotype and a metabolically active CD8 subset, without further viral reservoir extension. Persistence of low CD4/CD8 ratio and low nadir-CD4 counts seems to rely on different immune damage.The author(s) declare financial support was received for the research and/or publication of this article. This work was supported by grant CNS2023-144725 funded by MICIU/AEI/10.13039/501100011033 and, by “European Union NextGenerationEU/PRTR” and grant from the Fondo de Investigación Sanitaria (FIS; PI18/01216, PI20/00326 and PI21/00357) which are co-funded by Fondos Europeos para el Desarrollo Regional (FEDER) “A way to make Europe”; the Instituto de Salud Carlos III (FI19/00298 to VGR; CD19/00143 toÁB-R, CM19/00051 to IO-M and CP19/00146 to AR); the Consejerı́a de Transformación Económica, Industria, Conocimiento y Universidades (DOC_01646 to MP-B) and the Consejerı́a de Salud y Familias of Junta de Andalucı́a through the “Nicolás Monardes” (RC-0006–2021 to YP). The HIV BioBank is supported by Instituto de Salud Carlos III (PT20/00138) and Networking Research Center on Bioengineering, Biomaterials and Nanomedicine, CIBER-BBN (CB22/01/00041). CoRIS cohort is supported by CIBER - Consorcio Centro de Investigación Biomédica en Red (CB21/13/00091), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea—NextGenerationEU. AR and JP are also supported by CIBER-INF (CB21/13/00020). The funders had no role in the study design, data collection and interpretation, or the decision to submit the work for publication.Peer reviewedFrontiers MediaEuropean CommissionAgencia Estatal de Investigación (España)Ministerio de Ciencia, Innovación y Universidades (España)Instituto de Salud Carlos IIIJunta de AndalucíaConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202520252025info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/407739https://api.elsevier.com/content/abstract/scopus_id/105017101609reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016 (ISCIII)/PI18%2F01216info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI20%2F00326info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI21%2F00357info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI19%2F00298The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI https://doi.org/10.3389/fimmu.2025.1617674https://doi.org/10.3389/fimmu.2025.1617674Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/4077392026-05-22T06:33:51Z
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