Age-related decline in the in vitro and in vivo syntheses of anti-tetanus toxoid antibody in humans.

Abstract

Each of aged subjects (65 to 84 yr old) and adults (25 to 34 yr old) received a primary immunization with tetanus toxoid and was boosted after 6 wk. The mean titers of total and IgG anti-tetanus toxoid antibodies as determined by a passive hemagglutination procedure were significantly lower in the aged group than in the adult group 2 wk after booster immunization, when the responses reached a peak (p < 0.02). The aged subjects attained lower titers of total and IgG antibodies through the response to 10 wk. In addition, there was a more rapid fall-off of IgG antibody in the aged.In more than half of the donors, irrespective of age, there was an in vitro synthesis of IgG antibody by PBL without PWM stimulation before and 2 wk after booster immunization. However, no spontaneous synthesis of IgG antibody was observed in all of the aged donors and 6 of 11 adults at 4 wk after booster immunization.The magnitudes of IgG antibody quantities produced by in vitro PWM-stimulated PBL were significantly low in the aged when compared with adults at 2 and 4 wk post-booster immunization (p < 0.05). Moreover, the proportion of aged donors responding in the in vitro production of IgG antibody was also significantly decreased at 4 wk post-booster immunization (p < 0.05). In contrast, the mean quantities of total IgG produced in the adults and aged subjects were 263 ng/ml and 550 ng/ml at 2 wk after booster immunization (p < 0.05), and 245 ng/ml and 398 ng/ml at 4 wk (p > 0.05) after booster immunization, respectively.The impairment of tetanus toxoid-specific T helper activity was shown to account in part for an age-related decline of IgG antibody synthesis in vitro and presumably in vivo. Aged PBL produced a smaller amount of IgG antibody but a greater amount of total IgG than did adult PBL when stimulated in vitro by PWM, and aged T cells were depressed for the antigen-specific helper activity but enhanced for multispecific helper activity when compared with adults.