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Characterization of Human Mycobacterium bovis Bacille Calmette-Guérin-Reactive CD8 + T Cells

1999; American Society for Microbiology; Volume: 67; Issue: 10 Linguagem: Inglês

10.1128/iai.67.10.5223-5230.1999

1098-5522

Steven M. Smith, Adam S. Malin, T Pauline, Lukey, Sara E. Atkinson, Jean Content, Kris Huygen, Hazel M. Dockrell,

Immunodeficiency and Autoimmune Disorders

ABSTRACT Gamma interferon (IFN-γ)-secreting CD4 + T cells have long been established as an essential component of the protective immune response against Mycobacterium 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 cells are capable of acting as both IFN-γ secretors and cytotoxic T lymphocyte (CTL) effectors; however, their exact role in immunity against tuberculosis remains unclear. This study demonstrates the presence of Mycobacterium bovis BCG-reactive CD8 + T cells in healthy BCG-vaccinated donors and that these CD8 + T cells are potent cytokine producers as well as cytotoxic effector cells. Using FACScan analysis, we have shown that restimulation with live M. bovis BCG induced more CD8 + -T-cell activation than the soluble antigen purified protein derivative and that these cells are actively producing the type 1 cytokines IFN-γ and tumor necrosis factor alpha (TNF-α). These CD8 + T cells also contain the cytolytic granule perforin and are capable of acting as potent CTLs against M. bovis BCG-infected macrophages. 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. bovis BCG activated effector cells from these BCG-vaccinated donors, as expected, failed to recognize the 6-kDa ESAT-6 protein. The use of metabolic inhibitors and blocking antibodies revealed that the CD8 + T cells recognize antigen 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 immune response to tuberculosis infection.