title: Reduced naïve CD8(+) T-cell priming efficacy in elderly adults.
abstract: Aging is associated with impaired vaccine efficacy and increased susceptibility to infectious and malignant diseases. CD8(+) T-cells are key players in the immune response against pathogens and tumors. In aged mice, the dwindling naïve CD8(+) T-cell compartment is thought to compromise the induction of de novo immune responses, but no experimental evidence is yet available in humans. Here, we used an original in vitro assay based on an accelerated dendritic cell coculture system in unfractioned peripheral blood mononuclear cells to examine CD8(+) T-cell priming efficacy in human volunteers. Using this approach, we report that old individuals consistently mount quantitatively and qualitatively impaired de novo CD8(+) T-cell responses specific for a model antigen. Reduced CD8(+) T-cell priming capacity in vitro was further associated with poor primary immune responsiveness in vivo. This immune deficit likely arises as a consequence of intrinsic cellular defects and a reduction in the size of the naïve CD8(+) T-cell pool. Collectively, these findings provide new insights into the cellular immune insufficiencies that accompany human aging.
authors.affiliation: Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Sorbonne Universités, UPMC Univ Paris 06, DHU FAST, CR7, F-75013, Paris, France.|CIMI-Paris, INSERM, U1135, F-75013, Paris, France.
authors.forename: Olivia
authors.initials: O
authors.lastname: Briceño
authors.affiliation: Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Sorbonne Universités, UPMC Univ Paris 06, DHU FAST, CR7, F-75013, Paris, France.|CIMI-Paris, INSERM, U1135, F-75013, Paris, France.
authors.forename: Anna
authors.initials: A
authors.lastname: Lissina
authors.affiliation: Division of Infectious Diseases, University Hospital of Zurich, Zurich, Switzerland.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Wanke
authors.affiliation: INSERM, U1016, Institut Cochin, Paris, France.|CNRS, UMR8104, Paris, France.|Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Georgia
authors.initials: G
authors.lastname: Afonso
authors.affiliation: Division of Infectious Diseases, University Hospital of Zurich, Zurich, Switzerland.
authors.forename: Amrei
authors.initials: A
authors.lastname: von Braun
authors.affiliation: Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Sorbonne Universités, UPMC Univ Paris 06, DHU FAST, CR7, F-75013, Paris, France.|CIMI-Paris, INSERM, U1135, F-75013, Paris, France.
authors.forename: Kristanto
authors.initials: K
authors.lastname: Ragon
authors.affiliation: Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Sorbonne Universités, UPMC Univ Paris 06, DHU FAST, CR7, F-75013, Paris, France.|CIMI-Paris, INSERM, U1135, F-75013, Paris, France.
authors.forename: Tiphaine
authors.initials: T
authors.lastname: Miquel
authors.affiliation: Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff, Wales, UK.
authors.forename: Emma
authors.initials: E
authors.lastname: Gostick
authors.affiliation: Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Sorbonne Universités, UPMC Univ Paris 06, DHU FAST, CR7, F-75013, Paris, France.|CIMI-Paris, INSERM, U1135, F-75013, Paris, France.
authors.forename: Laura
authors.initials: L
authors.lastname: Papagno
authors.affiliation: Department of Virology, Medical University of Vienna, Vienna, Austria.
authors.forename: Karin
authors.initials: K
authors.lastname: Stiasny
authors.affiliation: Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff, Wales, UK.
authors.forename: David A
authors.initials: DA
authors.lastname: Price
authors.affiliation: INSERM, U1016, Institut Cochin, Paris, France.|CNRS, UMR8104, Paris, France.|Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.|Service de Diabétologie, Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Paris, France.
authors.forename: Roberto
authors.initials: R
authors.lastname: Mallone
authors.affiliation: Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Sorbonne Universités, UPMC Univ Paris 06, DHU FAST, CR7, F-75013, Paris, France.|CIMI-Paris, INSERM, U1135, F-75013, Paris, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Sauce
authors.affiliation: Division of Infectious Diseases, University Hospital of Zurich, Zurich, Switzerland.
authors.forename: Urs
authors.initials: U
authors.lastname: Karrer
authors.affiliation: Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Sorbonne Universités, UPMC Univ Paris 06, DHU FAST, CR7, F-75013, Paris, France.|CIMI-Paris, INSERM, U1135, F-75013, Paris, France.
authors.forename: Victor
authors.initials: V
authors.lastname: Appay
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology* / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D055815:Young Adult
keywords: aging; naïve CD8+ T-cells; priming