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dc.contributor.author | Calvet-Mirabent, Marta | |
dc.contributor.author | Sánchez-Cerrillo, Ildefonso | |
dc.contributor.author | Martín-Cófreces, Noa | |
dc.contributor.author | Martínez-Fleta, Pedro | |
dc.contributor.author | de la Fuente, Hortensia | |
dc.contributor.author | Tsukalov, Ilya | |
dc.contributor.author | Delgado-Arévalo, Cristina | |
dc.contributor.author | Calzada, María José | |
dc.contributor.author | de Los Santos, Ignacio | |
dc.contributor.author | Sanz, Jesús | |
dc.contributor.author | García-Fraile, Lucio | |
dc.contributor.author | Sánchez-Madrid, Francisco | |
dc.contributor.author | Alfranca, Arantzazu | |
dc.contributor.author | Muñoz-Fernández, María Ángeles | |
dc.contributor.author | Buzón, Maria J | |
dc.contributor.author | Martín-Gayo, Enrique | |
dc.date.accessioned | 2023-03-16T11:32:15Z | |
dc.date.available | 2023-03-16T11:32:15Z | |
dc.date.issued | 2022-07 | |
dc.identifier.citation | EBioMedicine. 2022 Jul;81:104090 | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/15644 | |
dc.description.abstract | Dysfunction of CD8+ T cells in people living with HIV-1 (PLWH) receiving anti-retroviral therapy (ART) has restricted the efficacy of dendritic cell (DC)-based immunotherapies against HIV-1. Heterogeneous immune exhaustion and metabolic states of CD8+ T cells might differentially associate with dysfunction. However, specific parameters associated to functional restoration of CD8+ T cells after DC treatment have not been investigated. We studied association of restoration of functional HIV-1-specific CD8+ T cell responses after stimulation with Gag-adjuvant-primed DC with ART duration, exhaustion, metabolic and memory cell subsets profiles. HIV-1-specific CD8+ T cell responses from a larger proportion of PLWH on long-term ART (more than 10 years; LT-ARTp) improved polyfunctionality and capacity to eliminate autologous p24+ infected CD4+ T cells in vitro. In contrast, functional improvement of CD8+ T cells from PLWH on short-term ART (less than a decade; ST-ARTp) after DC treatment was limited. This was associated with lower frequencies of central memory CD8+ T cells, increased co-expression of PD1 and TIGIT and reduced mitochondrial respiration and glycolysis induction upon TCR activation. In contrast, CD8+ T cells from LT-ARTp showed increased frequencies of TIM3+ PD1- cells and preserved induction of glycolysis. Treatment of dysfunctional CD8+ T cells from ST-ARTp with combined anti-PD1 and anti-TIGIT antibodies plus a glycolysis promoting drug restored their ability to eliminate infected CD4+ T cells. Together, our study identifies specific immunometabolic parameters for different PLWH subgroups potentially useful for future personalized DC-based HIV-1 vaccines. NIH (R21AI140930), MINECO/FEDER RETOS (RTI2018-097485-A-I00) and CIBERINF grants. | es_ES |
dc.description.sponsorship | NIH (R21AI140930), MINECO/FEDER RETOS (RTI2018-097485-A-I00) and CIBERINF grants. We would like to thank the NIH AIDS Reagent Pro- gram, Division of AIDS, NIAID, NIH for providing HIV-1 PTE Gag Peptide Pool from NIAID, DAIDS (cat #11057) for the study. We would also like to thank Alvaro Serrano Navarro, for his help on adapting the lin- ear mixed model previously described by Martin- C ofreces N. et al83 to our data. Graphical schematic rep- resentations were created with BioRender.com. EMG was supported by the NIH R21 program (R21AI140930), the Ramón y Cajal Program (RYC2018- 024374-I), the MINECO/FEDER RETOS program (RTI2018-097485-A-I00), by Comunidad de Madrid Talento Program (2017-T1/BMD-5396) and by Gilead becas de investigaci on (GLD19/00168). EMG and IDS are supported by Centro de Investigación Biomédica en Red (CIBERINF) de Enfermedades Infecciosas (CB21/ 13/00107). MCM was supported by NIH R21 program (R21AI140930), “La Caixa Banking Foundation (H20- 00218) and Gilead becas de investigaci on (GLD19/ 00168). MJB is supported by the Miguel Servet program funded by the Spanish Health Institute Carlos III (CP17/00179), the MINECO/FEDER RETOS program (RTI2018-101082-B-100), and Fundació La Marat o TV3 (201805-10FMTV3). EMG and MJB are both funded by “La Caixa Banking Foundation (H20-00218) and by REDINCOV grant from Fundació La Marat o TV3. FSM was supported by SAF2017-82886-R and PDI-2020- 120412RB-I00 grants from the Ministerio de Ciencia e Innovaci on, and HR17-00016 grant from “La Caixa Banking Foundation. HF was funded by PI21/01583 grant from Ministerio de Ciencia e Innovación, Instituto de Salud Carlos III. MJC was supported by PID2019- 104406RB-I00 from Ministerio de Ciencia e Innovación. ISC was funded by the CM21/00157 Rio- Hortega grant. IT was supported by grant for the pro- motion of research studies master-UAM 2021. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Elsevier | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject.mesh | HIV Infections | es_ES |
dc.subject.mesh | HIV-1 | es_ES |
dc.subject.mesh | Anti-Retroviral Agents | es_ES |
dc.subject.mesh | CD4-Positive T-Lymphocytes | es_ES |
dc.subject.mesh | CD8-Positive T-Lymphocytes | es_ES |
dc.subject.mesh | Dendritic Cells | es_ES |
dc.subject.mesh | Humans | es_ES |
dc.title | Antiretroviral therapy duration and immunometabolic state determine efficacy of ex vivo dendritic cell-based treatment restoring functional HIV-specific CD8+ T cells in people living with HIV. | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.identifier.pubmedID | 35665682 | es_ES |
dc.format.volume | 81 | es_ES |
dc.format.page | 104090 | es_ES |
dc.identifier.doi | 10.1016/j.ebiom.2022.104090 | es_ES |
dc.contributor.funder | Ministerio de Ciencia y Competitividad (España) | es_ES |
dc.contributor.funder | Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) | es_ES |
dc.contributor.funder | Comunidad de Madrid (España) | es_ES |
dc.contributor.funder | Gilead Sciences (Spain) | es_ES |
dc.contributor.funder | Fundación La Caixa | es_ES |
dc.contributor.funder | Instituto de Salud Carlos III | es_ES |
dc.contributor.funder | Ministerio de Ciencia e Innovación (España) | es_ES |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 2352-3964 | es_ES |
dc.relation.publisherversion | 10.1016/j.ebiom.2022.104090 | es_ES |
dc.identifier.journal | EBioMedicine | es_ES |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Biología de linfocitos B | es_ES |
dc.repisalud.institucion | CNIC | es_ES |
dc.rights.accessRights | open access | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/RTI2018-097485-A-I00 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/RYC2018-024374-I | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/2017-T1/BMD-5396 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/H20-00218 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/CP17/00179 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/RTI2018-101082-B-100 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/201805-10FMTV3 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/PI21/01583 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/PID2019-104406RB-I00 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/CM21/00157 | es_ES |