Characterization of human Mycobacterium bovis bacille Calmette-Guerin-reactive CD8(+) T cells

Gamma interferon (IFN-gamma)-secreting CD4(+) T cells have long been establ ished as an essential component of the protective immune response against M ycobacterium tuberculosis. It is now becoming evident from studies with the murine model of tuberculosis that an important role also exists for major histocompatibility complex (MHC) class I-restricted CD8(+) T cells. These c ells are capable of acting as both IFN-gamma secretors and cytotoxic T lymp hocyte (CTL) effecters; however, their exact role in immunity against tuber culosis remains unclear. This study demonstrates the presence of Mycobacter ium bovis BCG-reactive CD8(+) T cells in healthy BCG-vaccinated donors and that these CD8(+) T cells are potent cytokine producers as well as cytotoxi c effector cells. Using FACScan analysis,,ve have shown that restimulation with live M. bovis BCG induced more CD8(+)-T-cell activation than the solub le antigen purified protein derivative and that these cells are actively pr oducing the type 1 cytokines IFN-gamma and tumor necrosis factor alpha (TNF -alpha). These CD8(+) T cells also contain the cytolytic granule perforin a nd are capable of acting as potent CTLs against M. bovis BCG-infected macro phages. The mycobacterial antigens 85A and B (Ag85A and Ag85B, respectively ), and to a lesser extent the 19- and 38-kDa proteins, are major antigenic targets for these mycobacterium-specific CD8(+) T cells, while whole-M. bov is BCG activated effector cells from these BCG-vaccinated donors, as expect ed, failed to recognize the 6-kDa ESAT-6 protein. The use of metabolic inhi bitors and blocking antibodies revealed that the CD8(+) T cells recognize a ntigen processed and presented via the classical MHC class I pathway. These data suggest that CD8(+) T cells may play a critical role in the human imm une response to tuberculosis infection.