title: Preservation of Lymphopoietic Potential and Virus Suppressive Capacity by CD8+ T Cells in HIV-2-Infected Controllers.
abstract: Compared with HIV-1, HIV-2 infection is characterized by a larger proportion of slow or nonprogressors. A better understanding of HIV-2 pathogenesis should open new therapeutic avenues to establish control of HIV-1 replication in infected patients. In this study, we studied the production of CD8(+) T cells and their capacity for viral control in HIV-2 controllers from the French ANRS CO5 HIV-2 cohort. HIV-2 controllers display a robust capacity to support long-term renewal of the CD8(+) T cell compartment by preserving immune resources, including hematopoietic progenitors and thymic activity, which could contribute to the long-term maintenance of the CD8(+) T cell response and the avoidance of premature immune aging. Our data support the presence of HIV-2 Gag-specific CD8(+) T cells that display an early memory differentiation phenotype and robust effector potential in HIV-2 controllers. Accordingly, to our knowledge, we show for the first time that HIV-2 controllers possess CD8(+) T cells that show an unusually strong capacity to suppress HIV-2 infection in autologous CD4(+) T cells ex vivo, an ability that likely depends on the preservation of host immune resources. This effective and durable antiviral response probably participates in a virtuous circle, during which controlled viral replication permits the preservation of potent immune functions, thus preventing HIV-2 disease progression.
authors: Institut Pasteur, Unité HIV Inflammation et Persistance, Paris 75015, France;
authors: Mathieu
authors: 0000-0002-6867-4680
authors: M
authors: Angin
authors: Sorbonne Universités, Université Pierre et Marie Curie, Université Paris 06, DHU FAST, CR7, Centre d'Immunologie et des Maladies Infectieuses, INSERM U1135, Paris 75005, France; Nuffield Department of Medicine, Headington, Oxford OX3 7FZ, United Kingdom;
authors: Glenn
authors: G
authors: Wong
authors: Sorbonne Universités, Université Pierre et Marie Curie, Université Paris 06, DHU FAST, CR7, Centre d'Immunologie et des Maladies Infectieuses, INSERM U1135, Paris 75005, France;
authors: Laura
authors: 0000-0001-8084-2125
authors: L
authors: Papagno
authors: Institut Pasteur, Unité HIV Inflammation et Persistance, Paris 75015, France;
authors: Pierre
authors: P
authors: Versmisse
authors: Institut Pasteur, Unité HIV Inflammation et Persistance, Paris 75015, France;
authors: Annie
authors: A
authors: David
authors: Sorbonne Universités, Université Pierre et Marie Curie, Université Paris 06, DHU FAST, CR7, Centre d'Immunologie et des Maladies Infectieuses, INSERM U1135, Paris 75005, France;
authors: Charles
authors: C
authors: Bayard
authors: INSERM U1016, Institut Cochin, Cytokines and Viral Infections Team, Paris 75014, France; CNRS UMR 8104, Université Paris Descartes, Sorbonne Paris Cité, Paris 75014, France;
authors: Bénédicte
authors: B
authors: Charmeteau-De Muylder
authors: Centre de Méthodologie et de Gestion des Essais Cliniques de l'INSERM U1219, Virus de l'Immunodéficience Humaine, Hépatites Virales et Comorbidités, Épidémiologie Clinique et Santé Publique, Bordeaux 33076, France;
authors: Amel
authors: 0000-0001-9666-6808
authors: A
authors: Besseghir
authors: Centre de Méthodologie et de Gestion des Essais Cliniques de l'INSERM U1219, Virus de l'Immunodéficience Humaine, Hépatites Virales et Comorbidités, Épidémiologie Clinique et Santé Publique, Bordeaux 33076, France;
authors: Rodolphe
authors: R
authors: Thiébaut
authors: INSERM U1018, Centre de Recherche en Epidémiologie et Santé des Populations, Université Paris Sud, Le Kremlin Bicêtre 94270, France;
authors: Faroudy
authors: 0000-0002-3650-6105
authors: F
authors: Boufassa
authors: Institut Pasteur, Unité HIV Inflammation et Persistance, Paris 75015, France;
authors: Gianfranco
authors: 0000-0002-9862-983X
authors: G
authors: Pancino
authors: Sorbonne Universités, Université Pierre et Marie Curie, Université Paris 06, DHU FAST, CR7, Centre d'Immunologie et des Maladies Infectieuses, INSERM U1135, Paris 75005, France;
authors: Delphine
authors: D
authors: Sauce
authors: INSERM UMR 1184, Immunologie des Maladies Virales et Autoimmunes, Le Kremlin Bicêtre 94270, France; Assistance Publique-Hôpitaux de Paris, Service de Médecine Interne, Hôpitaux Universitaires, Le Kremlin Bicêtre 94270, France; Université Paris Sud, Le Kremlin Bicêtre 94270, France;
authors: Olivier
authors: O
authors: Lambotte
authors: Assistance Publique-Hôpitaux de Paris, Laboratoire de Virologie, Hôpital Bichat, Paris 75018, France;
authors: Françoise
authors: F
authors: Brun-Vézinet
authors: INSERM UMR 1137, Infections, Antimicrobiens, Modélisation, Evolution, Université Paris Diderot, Sorbonne Paris Cité, Paris 75018, France; and Assistance Publique-Hôpitaux de Paris, Service des Maladies Infectieuses et Tropicales, Hôpital Bichat, Paris 75018, France.
authors: Sophie
authors: 0000-0001-7879-6553
authors: S
authors: Matheron
authors: Nuffield Department of Medicine, Headington, Oxford OX3 7FZ, United Kingdom;
authors: Sarah L
authors: 0000-0001-5788-6998
authors: SL
authors: Rowland-Jones
authors: INSERM U1016, Institut Cochin, Cytokines and Viral Infections Team, Paris 75014, France; CNRS UMR 8104, Université Paris Descartes, Sorbonne Paris Cité, Paris 75014, France;
authors: Rémi
authors: 0000-0003-1146-660X
authors: R
authors: Cheynier
authors: Institut Pasteur, Unité HIV Inflammation et Persistance, Paris 75015, France; victor.appay@upmc.fr asier.saez-cirion@pasteur.fr.
authors: Asier
authors: A
authors: Sáez-Cirión
authors: Sorbonne Universités, Université Pierre et Marie Curie, Université Paris 06, DHU FAST, CR7, Centre d'Immunologie et des Maladies Infectieuses, INSERM U1135, Paris 75005, France; victor.appay@upmc.fr asier.saez-cirion@pasteur.fr.
authors: Victor
authors: V
authors: Appay
mesh_terms: D000328:Adult; D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D015658:HIV Infections / Q000175:diagnosis / Q000276:immunology* / Q000821:virology*; D015498:HIV-2 / Q000276:immunology*; D006801:Humans; D038041:Lymphopoiesis / Q000276:immunology*; D008297:Male; D008875:Middle Aged