Timing of appearance and disappearance of IFN and IL-2 induced natural immunity during ontogenetic development and aging.

The age-dependent modifications of both basal and lymphokine-induced natural killer (NK) activity were analyzed in Balb/c inbred mice by measuring either the percentage of specific lytic activity in a 51 Cr release assay or the percentage of cells capable of binding the YAC-1 target cells. The basal lytic activity of spleen cells is low at birth, then it increases progressively and reaches a peak between 5 and 8 weeks of age and decreases thereafter, displaying in 25-month-old mice only 10% of the NK activity found in young mice. The number of spleen cells capable of binding target cells is higher at birth and then it declines progressively-old mice show about 40% of the binding capacity found in young mice. Significant in vitro NK activation is obtained in spleen cells from 25-, 50- and 750-day-old mice by incubation with interleukin-2 (IL-2) (1.8-fold increase in 25- and 50-day-old mice and 2.6-fold increase in 750-day-old mice) while no effect is obtained in 15-day-old mice. The responsiveness to in vitro stimulation with interferon (IFN) is not present in 15-day-old mice, however it appears in a defective way at the age of 25 days, and reaches its highest level in 50- and 180-day-old mice, (3.5- and 4.5-fold increase), still remaining present in 630-day-old mice, (two-fold increase) but not in 750-day-old mice. The in vivo injection with IFN increases the spleen cell NK activity of 25- and 50-day-old mice (3.6- and 2.3-fold increase respectively) but not of 15- and 750-day-old mice. The present data here confirm the existence of age-dependent variations of spleen cell NK activity and suggest a similar sequential timing of appearance/disappearance of IL-2 and IFN responsive spleen cells during ontogenetic development and aging respectively.