Age decreases the capacity of mouse embryo fibroblasts to increase surface H-2 when stimulated with concanavalin A-induced splenocyte culture supernatant.

With increasing time in culture and increasing mitotic number there is a decreased sensitivity of BALB/c mouse embryo fibroblasts (MEF) to the effects of the culture supernatant from concanavalin A stimulated splenocytes. When exposed to culture supernatant in vitro for 16 h 'old' MEF (12 days in culture at 37 degrees C with three subcultures) showed less increase in class I major histocompatibility complex antigens (H-2Kd and H-2Dd) than 'young' MEF (up to 8 days in culture at 37 degrees C with two subcultures). The subculture number alone was not the cause of decreased sensitivity to culture supernatant, since MEF subcultured five times over 5 days in vitro did not exhibit it. We propose that the insensitivity to the major histocompatibility complex increasing effects of culture supernatant precedes cell senescence and discuss how it could contribute to depression of cell-mediated immunity in aged animals.