Kinetic analysis of Mycobacterium tuberculosis-specific cytokine production by PBMC in adults after BCG vaccination

Although bacille Calmette-Guérin (BCG) has been used worldwide as the only vaccine for tuberculosis, its protective efficacy in human adults is controversial. To investigate human immunological responses to Mycobacterium tuberculosis after BCG vaccination, we analyzed IFN-γ and IL-10 production by peripheral blood mononuclear cells (PBMC) from health-care workers five times throughout the year after BCG vaccination. Of 449 health-care workers, 36 (8.0%) were negative by the tuberculin skin test, and of these, 20 were vaccinated with BCG. Because all the subjects had received BCG vaccination as infants, the present vaccination was considered to be a revaccination. The cytokine responses of the vaccinated and control tuberculin skin-test-positive subjects (n = 6) were followed at 0, 2, 4, and 8 weeks and at 12 months. The mean IFN-γ production by PBMC when cultured with purified protein derivative (PPD) gradually increased, reached a peak at week 8, and then declined until 12 months, with four exceptions who showed no IFN-γ elevation. The IFN-γ level of the vaccinated group at week 0 was significantly lower than that of the controls. The mean IL-10 production in response to PPD reached a peak at week 2, and then declined to its lowest point at week 8. These results indicate that the BCG vaccine can induce a type I cytokine response to M. tuberculosis in most tuberculin skin-test-negative adults at week 8, suggesting the immunological efficacy of vaccination.