The aim of this study is to identify immune correlates of protection against tuberculosis induced by the current vaccine, Bacille Calmette Guerin (BCG). This knowledge should be valuable for developing and testing novel tuberculosis vaccines. Blood from 5675 10-week-old South African infants, routinely vaccinated with BCG at birth, was collected, processed, and stored. Subsequently, infants who have developed tuberculosis disease-"not protected by the vaccine"-and infants who have remained healthy despite exposure to adults with tuberculosis-"protected by the vaccine"-have been identified. Recall immune responses to mycobacterial antigens in whole blood samples from the infants have been elicited; the next step will be to retrieve stored blood of "unprotected" and "protected" infants and compare immunity induced by BCG in the two groups. To guide the immune analysis, various pilot studies are being conducted to characterize the vaccination-induced host response. Preliminary results indicate that BCG does indeed induce a potent CD8 T-cell response, with cytokine-producing or cytotoxic potential, in infants. An induction of FoxP3 mRNA expression in some mycobacteria-stimulated whole-blood samples is also being found, which suggests the presence of BCG-induced regulatory CD4 T cells. Finally, stimulation of whole blood with mycobacterial antigens has resulted in a consistent pattern of cytokine release: significant numbers of infants make either large amounts of the effector cytokine interferon-gamma, or large amounts of the regulatory cytokine interleukin-10, but not both. Tests will, therefore, be made to determine whether CD8 or regulatory CD4 T-cell responses, as well as "outlier" cytokine responses, are associated with vaccination-induced protection against tuberculosis.