title: IgE regulation and lymphokine patterns in aging humans.
abstract: IgE production declines with age, and allergic symptoms tend to improve. Aging therefore represents an in vivo model to study IgE regulation. We compared IgE production in older (> or = 60 years old) and young (15 to 30 years old) nonatopic individuals. Addition of exogenous interleukin-4 (IL-4) to mononuclear cells from older and young subjects induced equivalent amounts of IgE, indicating that IL-4 responsiveness is preserved in aging. After surface receptor stimulation with concanavalin A, IL-4 production by mononuclear cells from older subjects was approximately 50% as compared with the young, whereas interferon-gamma (IFN-gamma) production was reduced threefold (p = 0.008). By contrast, stimulation with phorbol esters and ionophore, which bypass surface receptor signaling, induced comparable amounts of IL-4 and IFN-gamma in older and young subjects. These data point to an impairment in T-cell membrane signal transduction in older individuals. This hypothesis was directly confirmed by showing that Ca+2 fluxes after CD3 crosslinking were significantly (p = 0.014) decreased in the older population. Our findings altogether suggest that an age-dependent T-cell activation defect may result in decreased availability of IL-4 and in the waning of IgE responses.
authors.affiliation: Children's Hospital/Department of Pediatrics, Harvard Medical School, Boston, MA 02115.
authors.forename: H
authors.initials: H
authors.lastname: al-Rayes
authors.forename: W
authors.initials: W
authors.lastname: Pachas
authors.forename: N
authors.initials: N
authors.lastname: Mirza
authors.forename: D J
authors.initials: DJ
authors.lastname: Ahern
authors.forename: R S
authors.initials: RS
authors.lastname: Geha
authors.forename: D
authors.initials: D
authors.lastname: Vercelli
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging / Q000276:immunology*; D017252:CD3 Complex / Q000032:analysis; D015220:Calcium Channels / Q000502:physiology; D006801:Humans; D007073:Immunoglobulin E / Q000502:physiology*; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008222:Lymphokines / Q000378:metabolism*; D008875:Middle Aged
chemical_list: D017252:CD3 Complex; D015220:Calcium Channels; D008222:Lymphokines; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma