title: Human NK cells display major phenotypic and functional changes over the life span.
abstract: Aging is generally associated with an increased predisposition to infectious diseases and cancers, related in part to the development of immune senescence, a process that affects all cell compartments of the immune system. Although many studies have investigated the effects of age on natural killer (NK) cells, their conclusions remain controversial because the diverse health status of study subjects resulted in discordant findings. To clarify this situation, we conducted the first extensive phenotypic and functional analysis of NK cells from healthy subjects, comparing NK cells derived from newborn (cord blood), middle-aged (18-60 years), old (60-80 years), and very old (80-100 years) subjects. We found that NK cells in cord blood displayed specific features associated with immaturity, including poor expression of KIR and LIR-1/ILT-2 and high expression of both NKG2A and IFN-gamma. NK cells from older subjects, on the other hand, preserved their major phenotypic and functional characteristics, but with their mature features accentuated. These include a profound decline of the CD56(bright) subset, a specific increase in LIR-1/ILT-2, and a perfect recovering of NK-cell function following IL2-activation in very old subjects. We conclude that the preservation of NK cell features until very advanced age may contribute to longevity and successful aging.
authors.affiliation: INSERM, UMR-S 945, F-75013, Paris, France.
authors.forename: Magali
authors.initials: M
authors.lastname: Le Garff-Tavernier
authors.forename: Vivien
authors.initials: V
authors.lastname: Béziat
authors.forename: Julie
authors.initials: J
authors.lastname: Decocq
authors.forename: Virginie
authors.initials: V
authors.lastname: Siguret
authors.forename: Frédérique
authors.initials: F
authors.lastname: Gandjbakhch
authors.forename: Eric
authors.initials: E
authors.lastname: Pautas
authors.forename: Patrice
authors.initials: P
authors.lastname: Debré
authors.forename: Hélène
authors.initials: H
authors.lastname: Merle-Beral
authors.forename: Vincent
authors.initials: V
authors.lastname: Vieillard
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002462:Cell Membrane / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000166:cytology* / Q000378:metabolism*; D008136:Longevity / Q000502:physiology*; D016131:Lymphocyte Subsets / Q000166:cytology / Q000378:metabolism; D008875:Middle Aged; D010641:Phenotype; D055607:Receptors, Natural Killer Cell / Q000378:metabolism
chemical_list: D055607:Receptors, Natural Killer Cell; D007371:Interferon-gamma