IMMUNIZATION WITH HEAT-KILLED MYCOBACTERIUM-VACCAE STIMULATES CD8(-CELLS SPECIFIC FOR MACROPHAGES INFECTED WITH MYCOBACTERIUM-TUBERCULOSIS() CYTOTOXIC T)

Immune responses to Mycobacterium tuberculosis are analyzed in mice wh ich have been immunized with Mycobacterium vaccae to examine novel way s of altering protective immunity against M. tuberculosis. The spleen cells of mice immunized with M. vaccae proliferate and secrete gamma i nterferon (IFN-gamma) in response to challenge with live M. tuberculos is in vitro. Immunization,vith M. vaccae results in the generation of CD8(+) T cells which kill syngeneic macrophages infected with M. tuber culosis. These effector cytotoxic T cells (CTL) are detectable in the spleen at 2 weeks after immunization with M. vaccae but cannot be foun d in splenocytes 3 to 6 weeks postimmunization. However, M. tuberculos is-specific CTL are revealed following restimulation in vitro with hea t-killed M. vaccae or M. tuberculosis, consistent,vith the activation of memory cells. These CD8(+) T cells secrete IFN-gamma and enhance th e production of interleukin 12 when cocultured with M. tuberculosis-in fected macrophages. It is suggested that CD8(+) T cells with a cytokin e secretion profile of the Tc1 class may themselves maintain the domin ance of a Th1-type cytokine response following immunization,vith M. va ccae. Heat-killed M. vaccae deserves attention as an alternative to at tenuated live mycobacterial vaccines.