PMID- 37800637 OWN - NLM STAT- MEDLINE DCOM- 20231221 LR - 20240226 IS - 1473-5571 (Electronic) IS - 0269-9370 (Linking) VI - 38 IP - 2 DP - 2024 Feb 1 TI - CD8 + T-cell priming is quantitatively but not qualitatively impaired in people with HIV-1 on antiretroviral therapy. PG - 161-166 LID - 10.1097/QAD.0000000000003746 [doi] AB - BACKGROUND: The induction of de novo CD8 + T-cell responses is essential for protective antiviral immunity, but this process is often impaired in people with HIV-1 (PWH). We investigated the extent to which the immune competence of naive CD8 + T cells, a key determinant of priming efficacy, could be preserved or restored in PWH via long-term antiretroviral therapy (ART). METHODS: We used flow cytometry, molecular analyses of gene transcription and telomere length, and a fully validated priming assay to characterize naive CD8 + T cells ex vivo and evaluate the induction of antigen-specific effector/memory CD8 + T cells in vitro , comparing age-matched healthy uninfected donors (HUDs), PWH on ART, and natural HIV-1 controllers (HICs). RESULTS: We found that naive CD8 + T cells were numerically reduced and exhibited a trend toward shorter telomere lengths in PWH on ART compared with HUDs and HICs. These features associated with impaired priming efficacy. However, we also found that naive CD8 + T cells were fully equipped proliferatively and transcriptionally in PWH on ART, enabling the generation of antigen-specific effector/memory CD8 + T cells with functional and phenotypic attributes comparable to those primed from HUDs. CONCLUSION: Our data suggest that naive CD8 + T cells in PWH on ART are intrinsically capable of generating functionally and phenotypically intact effector/memory CD8 + T cells in response to antigen, despite evidence of senescence and an overall numerical reduction that compromises priming efficacy relative to HUDs and HICs. CI - Copyright (c) 2023 Wolters Kluwer Health, Inc. All rights reserved. FAU - Cabral-Piccin, Mariela P AU - Cabral-Piccin MP AD - Universite de Bordeaux, CNRS UMR 5164, INSERM ERL 1303, ImmunoConcEpT, Bordeaux. AD - Sorbonne Universite, INSERM U1135, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, France. FAU - Briceno, Olivia AU - Briceno O AD - Sorbonne Universite, INSERM U1135, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, France. AD - Departamento de Investigacion en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas, Calzada de Tlalpan 4502, Colonia Seccion XVI, Tlalpan, Mexico City, Mexico. FAU - Papagno, Laura AU - Papagno L AD - Universite de Bordeaux, CNRS UMR 5164, INSERM ERL 1303, ImmunoConcEpT, Bordeaux. AD - Sorbonne Universite, INSERM U1135, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, France. FAU - Liouville, Benjamin AU - Liouville B AD - Sorbonne Universite, INSERM U1135, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, France. FAU - White, Eoghann AU - White E AD - Universite de Bordeaux, CNRS UMR 5164, INSERM ERL 1303, ImmunoConcEpT, Bordeaux. AD - Sorbonne Universite, INSERM U1135, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, France. FAU - Perdomo-Celis, Federico AU - Perdomo-Celis F AD - Institut Pasteur, Universite Paris Cite, Unite HIV Inflammation et Persistance. FAU - Autaa, Gaelle AU - Autaa G AD - Universite de Bordeaux, CNRS UMR 5164, INSERM ERL 1303, ImmunoConcEpT, Bordeaux. FAU - Volant, Stevenn AU - Volant S AD - Institut Pasteur, Universite Paris Cite, Bioinformatics and Biostatistics Hub, Paris, France. FAU - Llewellyn-Lacey, Sian AU - Llewellyn-Lacey S AD - Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, UK. FAU - Fromentin, Remi AU - Fromentin R AD - Centre de Recherche du CHUM and Department of Microbiology, Infectiology and Immunology, Universite de Montreal, Montreal, Quebec, Canada. FAU - Chomont, Nicolas AU - Chomont N AD - Centre de Recherche du CHUM and Department of Microbiology, Infectiology and Immunology, Universite de Montreal, Montreal, Quebec, Canada. FAU - Price, David A AU - Price DA AD - Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, UK. AD - Systems Immunity Research Institute, Cardiff University School of Medicine, Cardiff, UK. FAU - Saez-Cirion, Asier AU - Saez-Cirion A AD - Institut Pasteur, Universite Paris Cite, Unite HIV Inflammation et Persistance. AD - Institut Pasteur, Universite Paris Cite, Viral Reservoirs and Immune Control Unit, Paris. FAU - Lambotte, Olivier AU - Lambotte O AD - Universite Paris-Saclay, AP-HP Hopitaux Universitaires Paris Saclay, Service de Medecine Interne, Bicetre (UMR 1184), CEA (IDMIT Department, IBFJ), INSERM, Center for Immunology of Viral, Auto-Immune, Hematological and Bacterial Diseases (IMVA-HB), Le Kremlin Bicetre. FAU - Katlama, Christine AU - Katlama C AD - Infectious Diseases Department, Pitie-Salpetriere Hospital, AP-HP, Pierre Louis Epidemiology and Public Health Institute (iPLESP), INSERM 1136, Sorbonne Universite, Paris, France. FAU - Appay, Victor AU - Appay V AD - Universite de Bordeaux, CNRS UMR 5164, INSERM ERL 1303, ImmunoConcEpT, Bordeaux. AD - Sorbonne Universite, INSERM U1135, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, France. LA - eng PT - Journal Article DEP - 20231005 PL - England TA - AIDS JT - AIDS (London, England) JID - 8710219 SB - IM MH - Humans MH - *HIV Infections/drug therapy MH - *HIV-1 MH - CD8-Positive T-Lymphocytes MH - *HIV Seropositivity EDAT- 2023/10/06 12:44 MHDA- 2023/12/21 06:42 CRDT- 2023/10/06 07:24 PHST- 2023/12/21 06:42 [medline] PHST- 2023/10/06 12:44 [pubmed] PHST- 2023/10/06 07:24 [entrez] AID - 00002030-202402010-00005 [pii] AID - 10.1097/QAD.0000000000003746 [doi] PST - ppublish SO - AIDS. 2024 Feb 1;38(2):161-166. doi: 10.1097/QAD.0000000000003746. Epub 2023 Oct 5.