Human cytolytic and interferon γ-secreting CD8+ T lymphocytes specific for Mycobacterium tuberculosis
- Ajit Lalvani*,†,
- Roger Brookes*,†,‡,
- Robert J. Wilkinson§,¶,
- Adam S. Malin‖,
- Ansar A. Pathan*,
- Peter Andersen**,
- Hazel Dockrell‖,
- Geoffrey Pasvol¶, and
- Adrian V. S. Hill*
- *Molecular Immunology Group, Institute of Molecular Medicine, Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom; §Tuberculosis and Related Infections Unit, Royal Postgraduate Medical School, London W12 0NN, United Kingdom; ¶Department of Infection and Tropical Medicine, Imperial College School of Medicine, Northwick Park Hospital, London HA1 3UJ, United Kingdom; ‖Clinical Sciences, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E, United Kingdom; and **Tuberculosis Unit, Staatens Seruminstitut, Artileriweg 5, Copenhagen-S, Denmark DK2300
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Edited by Barry R. Bloom, Albert Einstein College of Medicine, Hasting-on-Hudson, NY, and approved October 28, 1997 (received for review July 11, 1997)
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 γ 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 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 against M. tuberculosis in humans and support current attempts to generate protective cytotoxic T lymphocyte responses against M. tuberculosis by vaccination.
Footnotes
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↵ † A.L. and R.B. contributed equally to this work.
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↵ ‡ To whom reprint requests should be addressed. e-mail: roger.brookes{at}ndm.ox.ac.uk.
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This paper was submitted directly (Track II) to the Proceedings Office.
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Abbreviations: BCG, Bacille Calmette-Guerin; MHC, major histocompatibility complex; CTL, cytotoxic T lymphocyte; ESAT-6, early secretory antigenic target 6; PBMCs, peripheral blood mononuclear cells; IGN-γ, interferon-γ; SFC, spot-forming cells; STCL, short-term cell line; BCL, B cell line; ELISPOT, enzyme-linked immunospot.
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↵ ** Zhang, M., Gong, J., Lin, Y., Boylen, C. T. & Barnes, P. F. American Association of Immunologists Joint Meeting, June 2–6, 1996, New Orleans, LA.
- Copyright © 1998, The National Academy of Sciences
