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Science 2 October 1998:
Vol. 282. no. 5386, pp. 121 - 125
DOI: 10.1126/science.282.5386.121
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Reports

An Antimicrobial Activity of Cytolytic T Cells Mediated by Granulysin

Steffen Stenger, * Dennis A. Hanson, Rachel Teitelbaum, Puneet Dewan, Kayvan R. Niazi, Christopher J. Froelich, Tomas Ganz, Sybille Thoma-Uszynski, Agustín Melián, Christian Bogdan, Steven A. Porcelli, Barry R. Bloom, Alan M. Krensky, Robert L. Modlin dagger

Cytolytic T lymphocytes (CTLs) kill intracellular pathogens by a granule-dependent mechanism. Granulysin, a protein found in granules of CTLs, reduced the viability of a broad spectrum of pathogenic bacteria, fungi, and parasites in vitro. Granulysin directly killed extracellular Mycobacterium tuberculosis, altering the membrane integrity of the bacillus, and, in combination with perforin, decreased the viability of intracellular M. tuberculosis. The ability of CTLs to kill intracellular M. tuberculosis was dependent on the presence of granulysin in cytotoxic granules, defining a mechanism by which T cells directly contribute to immunity against intracellular pathogens.

S. Stenger, P. Dewan, K. R. Niazi, T. Ganz, S. Thoma-Uszynski, R. L. Modlin, Divisions of Dermatology and Pulmonary Medicine, Department of Medicine, Department of Microbiology and Immunology and the Molecular Biology Institute, UCLA School of Medicine, Los Angeles, CA 90095, USA. D. A. Hanson and A. M. Krensky, Division of Immunology and Transplantation Biology, Department of Pediatrics, Stanford University, Stanford, CA 94305, USA. R. Teitelbaum and B. R. Bloom, Howard Hughes Medical Institute, Albert Einstein College of Medicine, Bronx, NY 10461, USA. C. J. Froelich, Evanston Northwestern Healthcare Research Institute and Evanston Hospital, Department of Medicine, Evanston, IL 60201, USA. A. Melián and S. A. Porcelli, Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital at Harvard Medical School, Boston, MA 02115, USA. C. Bogdan, Institut für Klinische Mikrobiologie, Immunologie und Hygiene, Universität Erlangen, D-91054 Erlangen, Germany.
*   Current address: Institut für Klinische Mikrobiologie, Immunologie und Hygiene, Universität Erlangen, D-91054 Erlangen, Germany.

dagger    To whom correspondence should be addressed: rmodlin{at}medicine.medsch.ucla.edu

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Infect. Immun. 70, 5167-5176
   Abstract »    Full Text »    PDF »
Multiple Chlamydiapneumoniae Antigens Prime CD8+ Tc1 Responses That Inhibit Intracellular Growth of This Vacuolar Pathogen.
B. Wizel, B. C. Starcher, B. Samten, Z. Chroneos, P. F. Barnes, J. Dzuris, Y. Higashimoto, E. Appella, and A. Sette (2002)
J. Immunol. 169, 2524-2535
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Selective expansion of perforin-positive CD8+ T cells by immature dendritic cells infected with live Bacillus Calmette-Guerin mycobacteria.
Y. Tsunetsugu-Yokota, H. Tamura, M. Tachibana, K. Ogata, M. Honda, and T. Takemori (2002)
J. Leukoc. Biol. 72, 115-124
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Induction of CD1-Restricted Immune Responses in Guinea Pigs by Immunization with Mycobacterial Lipid Antigens.
K. Hiromatsu, C. C. Dascher, K. P. LeClair, M. Sugita, S. T. Furlong, M. B. Brenner, and S. A. Porcelli (2002)
J. Immunol. 169, 330-339
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Identification by Mass Spectrometry of CD8+-T-Cell Mycobacterium tuberculosis Epitopes within the Rv0341 Gene Product.
D. C. Flyer, V. Ramakrishna, C. Miller, H. Myers, M. McDaniel, K. Root, C. Flournoy, V. H. Engelhard, D. H. Canaday, J. A. Marto, et al. (2002)
Infect. Immun. 70, 2926-2932
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Innate Immunity to Mycobacterium tuberculosis.
R. van Crevel, T. H. M. Ottenhoff, and J. W. M. van der Meer (2002)
Clin. Microbiol. Rev. 15, 294-309