Specificity of lymphocyte stimulation in vitro by microbial preparations: importance of antigen concentration

Blood mononuclear cells were stimulated in vitro by 7 different microbial preparations, and thymidine incorporation was investigated in 7 groups of persons sensitized to the microorganisms and in 7 groups of controls. The sensitized persons were: 18 BCG-vaccinated, 13 with previous Mycoplasma pneumoniae pneumonia, 22 who had serum antibodies to Herpes simplex virus, 14 with previous typhoid fever, 13 with previous acute pyelonephritis caused by Eschrerichia coli, 6 with previous Haemophilus influenzae meningitis, and 15 tetanus-vaccinated persons. Employing microbial preparations corresponding to the type of sensitization, higher responses were obtained with PPD, Mycoplasma pneumoniae, Herpes simplex virus, Salmonella typhi and tetanus toxoid in sensitized than in controls, but the responses to E. coli and H. influenzae were similar. In each experiment a dose titration of the microbial preparation was carried out. The best separation between sensitized and non-sensitized persons was obtained at low concentrations, giving submaximal stimulation. It is concluded that lymphocyte responses to many microbial preparations are combined of antigen-specific components and of responses to cross-reacting or polyclonally activating moieties, and that the antigen-specific response is best investigated at low concentrations of these preparations.