Reduced in Vitro Production of Anti-Tetanus Toxoid Antibody after Repeated in Vivo Immunization with Tetanus Toxoid

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Abstract
Lymphocytes from individuals booster-immunized with soluble tetanus toxoid synthesized anti-tetanus toxoid antibodies in vitro in the presence of pokeweed mitogen. The in vitro responsiveness initiated by day 14, peaked between days 20 and 40 and declined by days 60 to 80. Although the temporal kinetics of in vitro antibody production was similar in all individuals, the maximum levels of synthesis differed over an 8-fold range. The maximum quantity of anti-tetanus toxoid antibody synthesized in vitro after experimental immunization was correlated with the interval from prior booster immunization. Thus, cultures of B (0.4 × 106) and T (1.6 × 106) lymphocytes from individuals receiving the first immunization in ≥48 months synthesized up to 170 units of anti-tetanus toxoid antibody in vitro whereas individuals reboosted within 4 months of a prior immunization synthesized less than 40 units. This correlation was not observed with the in vitro synthesis of total IgG. The in vitro anti-tetanus toxoid antibody response appeared to reflect in vivo production of antibody in that individuals receiving the first immunization in ≥48 months showed the greatest increase in serum antibody levels whereas a second booster immunization 4 months later caused only a slight increase in serum levels of anti-tetanus toxoid antibody. The decreased in vitro responsiveness after repeated immunization was not correlated with the suppressive activity of radiosensitive T lymphocytes but appeared to reflect decreased function of the non-T lymphocyte fraction. Removal of phagocytic cells did not increase in vitro anti-tetanus toxoid antibody production by lymphocytes from reboosted individuals.