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Infection and Immunity, October 1999, p. 5223-5230, Vol. 67, No. 10
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Characterization of Human Mycobacterium
bovis Bacille Calmette-Guérin-Reactive CD8+
T Cells
Steven M.
Smith,1,*
Adam S.
Malin,1
Pauline T. ,
Lukey,2
Sara E.
Atkinson,1
Jean
Content,3
Kris
Huygen,4 and
Hazel M.
Dockrell1
Immunology Unit, Department of Infectious and
Tropical Diseases, London School of Hygiene & Tropical Medicine,
London,1 and Glaxo-Wellcome Research and
Development, Stevenage,2 United Kingdom, and
Departments of Virology3 and
Mycobacterial Immunology,4 Pasteur
Institute of Brussels, B1180 Brussels, Belgium
Received 22 March 1999/Returned for modification 5 May
1999/Accepted 5 July 1999
Gamma interferon (IFN-
)-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-
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-
and tumor necrosis factor alpha (TNF-
). 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.
*
Corresponding author. Mailing address: Immunology Unit,
Department of Infectious and Tropical Diseases, London School of
Hygiene & Tropical Medicine, Keppel St., London, WC1E 7HT, United
Kingdom. Phone: 44 (0)171 927 2832. Fax: 44 (0)171 637 4314. E-mail:
s.smith{at}lshtm.ac.uk.
Infection and Immunity, October 1999, p. 5223-5230, Vol. 67, No. 10
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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