Primary role of type I interferons for the induction of functionally optimal antigen-specific CD8 + T cells in HIV infection.

Autor:	Cabral-Piccin MP; Université de Bordeaux, CNRS UMR 5164, INSERM ERL 1303, ImmunoConcEpT, 33000, Bordeaux, France; Sorbonne Université, INSERM U1135, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), 75013, Paris, France., Papagno L; Université de Bordeaux, CNRS UMR 5164, INSERM ERL 1303, ImmunoConcEpT, 33000, Bordeaux, France; Sorbonne Université, INSERM U1135, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), 75013, Paris, France., Lahaye X; Institut Curie, INSERM U932, Immunity and Cancer Department, PSL Research University, 75005, Paris, France., Perdomo-Celis F; Institut Pasteur, Unité HIV Inflammation et Persistance, 75015, Paris, France., Volant S; Institut Pasteur, Hub Bioinformatique et Biostatistique, 75015, Paris, France., White E; Université de Bordeaux, CNRS UMR 5164, INSERM ERL 1303, ImmunoConcEpT, 33000, Bordeaux, France; Sorbonne Université, INSERM U1135, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), 75013, Paris, France., Monceaux V; Institut Pasteur, Unité HIV Inflammation et Persistance, 75015, Paris, France., Llewellyn-Lacey S; Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, CF14 4XN, UK., Fromentin R; Centre de Recherche du CHUM and Department of Microbiology, Infectiology and Immunology, Université de Montréal, Montreal, QC H2X 0A9, Canada., Price DA; Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, CF14 4XN, UK; Systems Immunity Research Institute, Cardiff University School of Medicine, Cardiff, CF14 4XN, UK., Chomont N; Centre de Recherche du CHUM and Department of Microbiology, Infectiology and Immunology, Université de Montréal, Montreal, QC H2X 0A9, Canada., Manel N; Institut Curie, INSERM U932, Immunity and Cancer Department, PSL Research University, 75005, Paris, France. Electronic address: nicolas.manel@curie.fr., Saez-Cirion A; Institut Pasteur, Unité HIV Inflammation et Persistance, 75015, Paris, France; Institut Pasteur, Université Paris Cité, Viral Reservoirs and Immune Control Unit, 75015, Paris, France. Electronic address: asier.saez-cirion@pasteur.fr., Appay V; Université de Bordeaux, CNRS UMR 5164, INSERM ERL 1303, ImmunoConcEpT, 33000, Bordeaux, France; Sorbonne Université, INSERM U1135, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), 75013, Paris, France; International Research Center of Medical Sciences, Kumamoto University, Kumamoto, 860-0811, Japan. Electronic address: victor.appay@immuconcept.org.
Jazyk:	angličtina
Zdroj:	EBioMedicine [EBioMedicine] 2023 May; Vol. 91, pp. 104557. Date of Electronic Publication: 2023 Apr 12.
DOI:	10.1016/j.ebiom.2023.104557
Abstrakt:	Background: CD8 + T cells equipped with a full arsenal of antiviral effector functions are critical for effective immune control of HIV-1. It has nonetheless remained unclear how best to elicit such potent cellular immune responses in the context of immunotherapy or vaccination. HIV-2 has been associated with milder disease manifestations and more commonly elicits functionally replete virus-specific CD8 + T cell responses compared with HIV-1. We aimed to learn from this immunological dichotomy and to develop informed strategies that could enhance the induction of robust CD8 + T cell responses against HIV-1. Methods: We developed an unbiased in vitro system to compare the de novo induction of antigen-specific CD8 + T cell responses after exposure to HIV-1 or HIV-2. The functional properties of primed CD8 + T cells were assessed using flow cytometry and molecular analyses of gene transcription. Findings: HIV-2 primed functionally optimal antigen-specific CD8 + T cells with enhanced survival properties more effectively than HIV-1. This superior induction process was dependent on type I interferons (IFNs) and could be mimicked via the adjuvant delivery of cyclic GMP-AMP (cGAMP), a known agonist of the stimulator of interferon genes (STING). CD8 + T cells elicited in the presence of cGAMP were polyfunctional and highly sensitive to antigen stimulation, even after priming from people living with HIV-1. Interpretation: HIV-2 primes CD8 + T cells with potent antiviral functionality by activating the cyclic GMP-AMP synthase (cGAS)/STING pathway, which results in the production of type I IFNs. This process may be amenable to therapeutic development via the use of cGAMP or other STING agonists to bolster CD8 + T cell-mediated immunity against HIV-1. Funding: This work was funded by INSERM, the Institut Curie, and the University of Bordeaux (Senior IdEx Chair) and by grants from Sidaction (17-1-AAE-11097, 17-1-FJC-11199, VIH2016126002, 20-2-AEQ-12822-2, and 22-2-AEQ-13411), the Agence Nationale de la Recherche sur le SIDA (ECTZ36691, ECTZ25472, ECTZ71745, and ECTZ118797), and the Fondation pour la Recherche Médicale (EQ U202103012774). D.A.P. was supported by a Wellcome Trust Senior Investigator Award (100326/Z/12/Z). Competing Interests: Declaration of interests N.M. is a cofounder of Stimunity, a company that develops cGAMP-loaded VLPs. A.S.C has received honoraria from MSD and Gilead for lectures. F.P-C is an inventor on a patent application by the Institut Pasteur (Method for reprogramming CD8+ T cells to enhance their therapeutic potential and applications thereof, US 63/301,532). (Copyright © 2023. Published by Elsevier B.V.)
Databáze:	MEDLINE
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