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Science 13 June 1997:
Vol. 276. no. 5319, pp. 1684 - 1687
DOI: 10.1126/science.276.5319.1684
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Reports

Differential Effects of Cytolytic T Cell Subsets on Intracellular Infection

Steffen Stenger, Richard J. Mazzaccaro, Koichi Uyemura, Sungae Cho, Peter F. Barnes, Jean-Pierre Rosat, Alessandro Sette, Michael B. Brenner, Steven A. Porcelli, Barry R. Bloom, Robert L. Modlin *

In analyzing mechanisms of protection against intracellular infections, a series of human CD1-restricted T cell lines of two distinct phenotypes were derived. Both CD4-CD8- (double-negative) T cells and CD8+ T cells efficiently lysed macrophages infected with Mycobacterium tuberculosis. The cytotoxicity of CD4-CD8- T cells was mediated by Fas-FasL interaction and had no effect on the viability of the mycobacteria. The CD8+ T cells lysed infected macrophages by a Fas-independent, granule-dependent mechanism that resulted in killing of bacteria. These data indicate that two phenotypically distinct subsets of human cytolytic T lymphocytes use different mechanisms to kill infected cells and contribute in different ways to host defense against intracellular infection.

S. Stenger, K. Uyemura, S. Cho, R. L. Modlin, Division of Dermatology and Department of Microbiology and Immunology, University of California Los Angeles School of Medicine, Los Angeles, CA 90095, USA.
R. J. Mazzaccaro and B. R. Bloom, Howard Hughes Medical Institute, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
P. F. Barnes, Department of Medicine, University of Southern California School of Medicine, Los Angeles, CA 90033, USA.
J.-P. Rosat, M. B. Brenner, S. A. Porcelli, Department of Rheumatology and Immunology, Brigham and Women's Hospital, Boston, MA 02115, USA.
A. Sette, Department of Immunology, Cytel Corporation, San Diego, CA 92121, USA.
*   To whom correspondence should be addressed. E-mail: rmodlin{at}medicine.medsch.ucla.edu

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   Abstract »    Full Text »    PDF »
Bactericidal and Tumoricidal Activities of Synthetic Peptides Derived from Granulysin.
Z. Wang, E. Choice, A. Kaspar, D. Hanson, S. Okada, S.-C. Lyu, A. M. Krensky, and C. Clayberger (2000)
J. Immunol. 165, 1486-1490
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Mycobacterium tuberculosis-Reactive CD8+ T Lymphocytes: The Relative Contribution of Classical Versus Nonclassical HLA Restriction.
D. M. Lewinsohn, A. L. Briden, S. G. Reed, K. H. Grabstein, and M. R. Alderson (2000)
J. Immunol. 165, 925-930
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IL-10 Converts Human Dendritic Cells into Macrophage-Like Cells with Increased Antibacterial Activity Against Virulent Mycobacterium tuberculosis.
D. Fortsch, M. Rollinghoff, and S. Stenger (2000)
J. Immunol. 165, 978-987
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CD8+ CTL from Lungs of Mycobacterium tuberculosis-Infected Mice Express Perforin In Vivo and Lyse Infected Macrophages.
N. V. Serbina, C.-C. Liu, C. A. Scanga, and J. L. Flynn (2000)
J. Immunol. 165, 353-363
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Lethal Granuloma Disintegration in Mycobacteria-Infected TNFRp55-/- Mice Is Dependent on T Cells and IL-12.
S. Ehlers, S. Kutsch, E. M. Ehlers, J. Benini, and K. Pfeffer (2000)
J. Immunol. 165, 483-492
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Adaptive Immunity and Enhanced CD8+ T Cell Response to Listeria monocytogenes in the Absence of Perforin and IFN-{gamma}.
V. P. Badovinac and J. T. Harty (2000)
J. Immunol. 164, 6444-6452
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Identification and Characterization of Murine Cytotoxic T Cells That Kill Mycobacterium tuberculosis.
C. L. Silva and D. B. Lowrie (2000)
Infect. Immun. 68, 3269-3274
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Evidence for Human CD4+ T Cells in the CD1-Restricted Repertoire: Derivation of Mycobacteria-Reactive T Cells from Leprosy Lesions.
P. A. Sieling, M.-T. Ochoa, D. Jullien, D. S. Leslie, S. Sabet, J.-P. Rosat, A. E. Burdick, T. H. Rea, M. B. Brenner, S. A. Porcelli, et al. (2000)
J. Immunol. 164, 4790-4796
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Intersection of Group I CD1 Molecules and Mycobacteria in Different Intracellular Compartments of Dendritic Cells.
U. E. Schaible, K. Hagens, K. Fischer, H. L. Collins, and S. H. E. Kaufmann (2000)
J. Immunol. 164, 4843-4852
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Relative contributions of distinct MHC class I-dependent cell populations in protection to tuberculosis infection in mice.
A. O. Sousa, R. J. Mazzaccaro, R. G. Russell, F. K. Lee, O. C. Turner, S. Hong, L. Van Kaer, and B. R. Bloom (2000)
PNAS 97, 4204-4208
   Abstract »    Full Text »    PDF »
Self-Recognition of Cd1 by {gamma}/{delta} T Cells: Implications for Innate Immunity.
F. M. Spada, E. P. Grant, P. J. Peters, M. Sugita, A. Melian, D. S. Leslie, H. K. Lee, E. van Donselaar, D. A. Hanson, A. M. Krensky, et al. (2000)
J. Exp. Med. 191, 937-948
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Bacterial Proteins Can Be Processed by Macrophages in a Transporter Associated with Antigen Processing-Independent, Cysteine Protease-Dependent Manner for Presentation by MHC Class I Molecules.
D. J. Campbell, T. Serwold, and N. Shastri (2000)
J. Immunol. 164, 168-175
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ATP-Induced Killing of Virulent Mycobacterium tuberculosis Within Human Macrophages Requires Phospholipase D.
D. J. Kusner and J. Adams (2000)
J. Immunol. 164, 379-388
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Mycobacterial infection of macrophages results in membrane-permeable phagosomes.
R. Teitelbaum, M. Cammer, M. L. Maitland, N. E. Freitag, J. Condeelis, and B. R. Bloom (1999)
PNAS 96, 15190-15195
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The In Vivo Fate of APCs Displaying Minor H Antigen and/or MHC Differences Is Regulated by CTLs Specific for Immunodominant Class I-Associated Epitopes.
V. Loyer, P. Fontaine, S. Pion, F. Hetu, D.-C. Roy, and C. Perreault (1999)
J. Immunol. 163, 6462-6467
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Conservation of a CD1 Multigene Family in the Guinea Pig.
C. C. Dascher, K. Hiromatsu, J. W. Naylor, P. P. Brauer, K. A. Brown, J. R. Storey, S. M. Behar, E. S. Kawasaki, S. A. Porcelli, M. B. Brenner, et al. (1999)
J. Immunol. 163, 5478-5488
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Identification of Promiscuous Epitopes from the Mycobacterial 65-Kilodalton Heat Shock Protein Recognized by Human CD4+ T Cells of the Mycobacterium leprae Memory Repertoire.
A. S. Mustafa, K. E. A. Lundin, R. H. Meloen, T. M. Shinnick, and F. Oftung (1999)
Infect. Immun. 67, 5683-5689
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Viral-Specific Cytotoxic T Lymphocytes Lyse Human Immunodeficiency Virus-Infected Primary T Lymphocytes by the Granule Exocytosis Pathway.
P. Shankar, Z. Xu, and J. Lieberman (1999)
Blood 94, 3084-3093
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CD1 Expression in Human Atherosclerosis : A Potential Mechanism for T Cell Activation by Foam Cells.
A. Melian, Y.-J. Geng, G. K. Sukhova, P. Libby, and S. A. Porcelli (1999)
Am. J. Pathol. 155, 775-786
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CTLA-4 Blockade Enhances the Immune Response Induced by Mycobacterial Infection but Does Not Lead to Increased Protection.
J. Kirman, K. McCoy, S. Hook, M. Prout, B. Delahunt, I. Orme, A. Frank, and G. Le Gros (1999)
Infect. Immun. 67, 3786-3792
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