Human cytolytic and interferon gamma-secreting CD8+ T lymphocytes specific for Mycobacterium tuberculosis

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,...

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Published in:Proceedings of the National Academy of Sciences - PNAS Vol. 95; no. 1; p. 270
Main Authors: Lalvani, A, Brookes, R, Wilkinson, R J, Malin, A S, Pathan, A A, Andersen, P, Dockrell, H, Pasvol, G, Hill, A V
Format: Journal Article
Language:English
Published: United States 06.01.1998
Subjects:
Adult
Amino Acid Sequence
Antigens, Bacterial - metabolism
Bacterial Proteins
CD8-Positive T-Lymphocytes - metabolism
CD8-Positive T-Lymphocytes - microbiology
Histocompatibility Testing
Humans
Interferon-gamma - metabolism
Molecular Sequence Data
Mycobacterium tuberculosis
T-Lymphocytes, Regulatory - metabolism
Tuberculosis - immunology
Tuberculosis - metabolism
ISSN:0027-8424
Online Access:Get more information
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Summary: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.
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ISSN:0027-8424
DOI:10.1073/pnas.95.1.270