Human cytolytic and interferon γ-secreting CD8+T lymphocytes specific forMycobacterium tuberculosis

Protective immunity toMycobacterium tuberculosisis poorly understood, but mounting evidence, at least in animal models, implicates major histocompatibility complex class I-restricted CD8+T cells as an essential component. By using a highly sensitive assay for single cell interferon γ release, we screened an array ofM. tuberculosisantigen-derived peptides congruent with HLA class I allele-specific motifs. We identified CD8+T cells specific for epitopes in the early secretory antigenic target 6 during active tuberculosis, after clinical recovery and in healthy contacts. Unrestimulated cells exhibited peptide-specific interferon γ secretion, whereas lines or clones recognized endogenously processed antigen and showed cytolytic activity. These results provide direct evidence for the involvement of CD8+cytotoxic T lymphocytes in host defense againstM. tuberculosisin humans and support current attempts to generate protective cytotoxic T lymphocyte responses againstM. tuberculosisby vaccination.