Mode of immunopotentiating action of BCG: persistence and spread of BCG infection.

The mode of action of BCG, strain Japan was investigated using the immune response to sheep red blood cells (SRBC) as an indicator system. When SRBC were injected into the BCG-primed foot pad, the direct plaque forming cells (PFC) and the effector cells responsible for delayed type hypersensitivity (PTH) were produced in various lymphoid organs widely distributed. Furthermore, bacterial counts in the draining popliteal lymph node and the spleen in the mice inoculated with BCG into the hind foot pad suggested that a local infection with BCG has spread to a generalized systemic infection of lymphoid tissues with time. Enhancement of DTH response to SRBC was induced when the mice previously infected with BCG were inmunized with SRBC mixed with purified protein derivative (PPD). These findings suggested that nonspecific augmentation of immune response with BCG was due to a generalized systemic activation of lymphoid system by BCG infection and the long lasting effect of immunopotentiation with BCG was due to persisting BCG infection in the lymphoid tissues.