IgE regulation and lymphokine patterns in aging humans.
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.
al-Rayes
H
H
Children's Hospital/Department of Pediatrics, Harvard Medical School, Boston, MA 02115.
Pachas
W
W
Mirza
N
N
Ahern
D J
DJ
Geha
R S
RS
Vercelli
D
D
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
D017252:CD3 Complex; D015220:Calcium Channels; D008222:Lymphokines; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma