title: Human cytolytic and interferon gamma-secreting CD8+ T lymphocytes specific for Mycobacterium tuberculosis.
abstract: Protective immunity to Mycobacterium tuberculosis is 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 gamma release, we screened an array of M. tuberculosis antigen-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 gamma 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 against M. tuberculosis in humans and support current attempts to generate protective cytotoxic T lymphocyte responses against M. tuberculosis by vaccination.
authors.affiliation: Molecular Immunology Group, Institute of Molecular Medicine, Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom.
authors.forename: A
authors.initials: A
authors.lastname: Lalvani
authors.forename: R
authors.initials: R
authors.lastname: Brookes
authors.forename: R J
authors.initials: RJ
authors.lastname: Wilkinson
authors.forename: A S
authors.initials: AS
authors.lastname: Malin
authors.forename: A A
authors.initials: AA
authors.lastname: Pathan
authors.forename: P
authors.initials: P
authors.lastname: Andersen
authors.forename: H
authors.initials: H
authors.lastname: Dockrell
authors.forename: G
authors.initials: G
authors.lastname: Pasvol
authors.forename: A V
authors.initials: AV
authors.lastname: Hill
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000378:metabolism; D001426:Bacterial Proteins; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000382:microbiology*; D006650:Histocompatibility Testing; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism; D014376:Tuberculosis / Q000276:immunology* / Q000378:metabolism
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D007371:Interferon-gamma