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,
Departments of
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Molecular Genetics and Biochemistry and
Medicine, and
Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261
CD8+ T lymphocytes have been implicated in the protective immune response against human and murine tuberculosis. However, the functional role that this cell subset plays during the resolution of infection remains controversial. In this study, we demonstrate the presence of Mycobacterium tuberculosis-specific CD8+ CTL in the lungs and lung-draining lymph nodes of mice infected with M. tuberculosis via the aerosol or i.v. route. These cells expressed perforin in vivo and specifically recognized and lysed M. tuberculosis-infected macrophages in a perforin-dependent manner after a short period of in vitro restimulation. The efficiency of lysis of infected macrophages was dependent upon the time allowed for interaction between macrophage and M. tuberculosis bacilli. Recognition of infected targets by CD8+ CTL was ß2-microglobulin and MHC class I dependent and was not CD1d restricted. The presented data indicate that CD8+ T cells contribute to the protective immune response during M. tuberculosis infection by exerting cytotoxic function and lysing infected macrophages.
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C. A. Scanga, V. P. Mohan, K. Tanaka, D. Alland, J. L. Flynn, and J. Chan The Inducible Nitric Oxide Synthase Locus Confers Protection against Aerogenic Challenge of Both Clinical and Laboratory Strains of Mycobacterium tuberculosis in Mice Infect. Immun., December 1, 2001; 69(12): 7711 - 7717. [Abstract] [Full Text] [PDF]
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 E. D. Chan, J. Chan, and N. W. Schluger What is the Role of Nitric Oxide in Murine and Human Host Defense against Tuberculosis? . Current Knowledge Am. J. Respir. Cell Mol. Biol., November 1, 2001; 25(5): 606 - 612. [Abstract] [Full Text] [PDF]
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I. M. Orme The search for new vaccines against tuberculosis J. Leukoc. Biol., July 1, 2001; 70(1): 1 - 10. [Abstract] [Full Text] [PDF]
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N. V. Serbina and J. L. Flynn CD8+ T Cells Participate in the Memory Immune Response to Mycobacterium tuberculosis Infect. Immun., July 1, 2001; 69(7): 4320 - 4328. [Abstract] [Full Text] [PDF]
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H. Shams, B. Wizel, S. E. Weis, B. Samten, and P. F. Barnes Contribution of CD8+ T Cells to Gamma Interferon Production in Human Tuberculosis Infect. Immun., May 1, 2001; 69(5): 3497 - 3501. [Abstract] [Full Text] [PDF]
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M. Gonzalez-Juarrero, O. C. Turner, J. Turner, P. Marietta, J. V. Brooks, and I. M. Orme Temporal and Spatial Arrangement of Lymphocytes within Lung Granulomas Induced by Aerosol Infection with Mycobacterium tuberculosis Infect. Immun., March 1, 2001; 69(3): 1722 - 1728. [Abstract] [Full Text] [PDF]
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J. Turner, C. D. D'Souza, J. E. Pearl, P. Marietta, M. Noel, A. A. Frank, R. Appelberg, I. M. Orme, and A. M. Cooper CD8- and CD95/95L-Dependent Mechanisms of Resistance in Mice with Chronic Pulmonary Tuberculosis Am. J. Respir. Cell Mol. Biol., February 1, 2001; 24(2): 203 - 209. [Abstract] [Full Text]
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J. E. Wigginton and D. Kirschner A Model to Predict Cell-Mediated Immune Regulatory Mechanisms During Human Infection with Mycobacterium tuberculosis J. Immunol., February 1, 2001; 166(3): 1951 - 1967. [Abstract] [Full Text] [PDF]
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 S. Cho, V. Mehra, S. Thoma-Uszynski, S. Stenger, N. Serbina, R. J. Mazzaccaro, J. L. Flynn, P. F. Barnes, S. Southwood, E. Celis, et al. Antimicrobial activity of MHC class I-restricted CD8+ T cells in human tuberculosis PNAS, October 12, 2000; (2000) 210391497. [Abstract] [Full Text]
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C. A. Scanga, V.P. Mohan, K. Yu, H. Joseph, K. Tanaka, J. Chan, and J. L. Flynn Depletion of CD4+ T Cells Causes Reactivation of Murine Persistent Tuberculosis Despite Continued Expression of Interferon {gamma} and Nitric Oxide Synthase 2 J. Exp. Med., July 31, 2000; 192(3): 347 - 358. [Abstract] [Full Text] [PDF]
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S. Cho, V. Mehra, S. Thoma-Uszynski, S. Stenger, N. Serbina, R. J. Mazzaccaro, J. L. Flynn, P. F. Barnes, S. Southwood, E. Celis, et al. Antimicrobial activity of MHC class I-restricted CD8+ T cells in human tuberculosis PNAS, October 24, 2000; 97(22): 12210 - 12215. [Abstract] [Full Text] [PDF]
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