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, Yet Succumb to Tuberculosis1
*
Department of Molecular Genetics and Biochemistry, and
Central Animal Facilities, University of Pittsburgh School of Medicine, Pittsburgh, PA 15206; and
Howard Hughes Medical Institute, Albert Einstein College of Medicine, Bronx, NY 10461
CD4 T cells are important in the protective immune response against
tuberculosis. Two mouse models deficient in CD4 T cells were used to
examine the mechanism by which these cells participate in protection
against Mycobacterium tuberculosis challenge. Transgenic
mice deficient in either MHC class II or CD4 molecules demonstrated
increased susceptibility to M. tuberculosis, compared
with wild-type mice. MHC class II-/- mice were more
susceptible than CD4-/- mice, as measured by survival
following M. tuberculosis challenge, but the relative
resistance of CD4-/- mice did not appear to be due to
increased numbers of CD4-8- (double-negative)
T cells. Analysis of in vivo IFN-
production in the lungs of
infected mice revealed that both mutant mouse strains were only
transiently impaired in their ability to produce IFN- following
infection. At 2 wk postinfection, IFN- production, assessed by
RT-PCR and intracellular cytokine staining, in the mutant mice was
reduced by >50% compared with that in wild-type mice. However, by 4
wk postinfection, both mutant and wild-type mice had similar levels of
IFN- mRNA and protein production. In CD4 T cell-deficient mice,
IFN- production was due to CD8 T cells. Thus, the importance of
IFN- production by CD4 T cells appears to be early in infection,
lending support to the hypothesis that early events in M.
tuberculosis infection are crucial determinants of the course
of infection.
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N. Boechat, F. Bouchonnet, M. Bonay, A. Grodet, V. Pelicic, B. Gicquel, and A. J. Hance Culture at High Density Improves the Ability of Human Macrophages to Control Mycobacterial Growth J. Immunol., May 15, 2001; 166(10): 6203 - 6211. [Abstract] [Full Text] [PDF]
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C. G. Feng, C. Demangel, A. T. Kamath, M. Macdonald, and W. J. Britton Dendritic cells infected with Mycobacterium bovis bacillus Calmette Guerin activate CD8+ T cells with specificity for a novel mycobacterial epitope Int. Immunol., April 1, 2001; 13(4): 451 - 458. [Abstract] [Full Text] [PDF]
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J. C. Leemans, N. P. Juffermans, S. Florquin, N. van Rooijen, M. J. Vervoordeldonk, A. Verbon, S. J. H. van Deventer, and T. van der Poll Depletion of Alveolar Macrophages Exerts Protective Effects in Pulmonary Tuberculosis in Mice J. Immunol., April 1, 2001; 166(7): 4604 - 4611. [Abstract] [Full Text] [PDF]
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V. Nagabhushanam and C. Cheers Non-Major Histocompatibility Complex Control of Antibody Isotype and Th1 versus Th2 Cytokines during Experimental Infection of Mice with Mycobacterium avium Infect. Immun., March 1, 2001; 69(3): 1708 - 1713. [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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T. Mogues, M. E. Goodrich, L. Ryan, R. LaCourse, and R. J. North The Relative Importance of T Cell Subsets in Immunity and Immunopathology of Airborne Mycobacterium tuberculosis Infection in Mice J. Exp. Med., February 5, 2001; 193(3): 271 - 280. [Abstract] [Full Text] [PDF]
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K. A. Bodnar, N. V. Serbina, and J. L. Flynn Fate of Mycobacterium tuberculosis within Murine Dendritic Cells Infect. Immun., February 1, 2001; 69(2): 800 - 809. [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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Y. A. W. Skeiky, P. J. Ovendale, S. Jen, M. R. Alderson, D. C. Dillon, S. Smith, C. B. Wilson, I. M. Orme, S. G. Reed, and A. Campos-Neto T Cell Expression Cloning of a Mycobacterium tuberculosis Gene Encoding a Protective Antigen Associated with the Early Control of Infection J. Immunol., December 15, 2000; 165(12): 7140 - 7149. [Abstract] [Full Text] [PDF]
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H.-J. Ullrich, W. L. Beatty, and D. G. Russell Interaction of Mycobacterium avium-Containing Phagosomes with the Antigen Presentation Pathway J. Immunol., December 1, 2000; 165(11): 6073 - 6080. [Abstract] [Full Text] [PDF]
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H. M. Dockrell, S. Brahmbhatt, B. D. Robertson, S. Britton, U. Fruth, N. Gebre, M. Hunegnaw, R. Hussain, R. Manandhar, L. Murillo, et al. A Postgenomic Approach to Identification of Mycobacterium leprae-Specific Peptides as T-Cell Reagents Infect. Immun., October 1, 2000; 68(10): 5846 - 5855. [Abstract] [Full Text] [PDF]
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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., August 7, 2000; 192(3): 347 - 358. [Abstract] [Full Text] [PDF]
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N. V. Serbina, C.-C. Liu, C. A. Scanga, and J. L. Flynn CD8+ CTL from Lungs of Mycobacterium tuberculosis-Infected Mice Express Perforin In Vivo and Lyse Infected Macrophages J. Immunol., July 1, 2000; 165(1): 353 - 363. [Abstract] [Full Text] [PDF]
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C. M. Bosio, D. Gardner, and K. L. Elkins Infection of B Cell-Deficient Mice with CDC 1551, a Clinical Isolate of Mycobacterium tuberculosis: Delay in Dissemination and Development of Lung Pathology J. Immunol., June 15, 2000; 164(12): 6417 - 6425. [Abstract] [Full Text] [PDF]
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A. O. Sousa, R. J. Mazzaccaro, R. G. Russell, F. K. Lee, O. C. Turner, S. Hong, L. Van Kaer, and B. R. Bloom Relative contributions of distinct MHC class I-dependent cell populations in protection to tuberculosis infection in mice PNAS, April 11, 2000; 97(8): 4204 - 4208. [Abstract] [Full Text] [PDF]
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N. V. Serbina and J. L. Flynn Early Emergence of CD8+ T Cells Primed for Production of Type 1 Cytokines in the Lungs of Mycobacterium tuberculosis-Infected Mice Infect. Immun., August 1, 1999; 67(8): 3980 - 3988. [Abstract] [Full Text] [PDF]
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C. Manca, L. Tsenova, A. Bergtold, S. Freeman, M. Tovey, J. M. Musser, C. E. Barry III, V. H. Freedman, and G. Kaplan Virulence of a Mycobacterium tuberculosis clinical isolate in mice is determined by failure to induce Th1 type immunity and is associated with induction of IFN-alpha /beta PNAS, May 8, 2001; 98(10): 5752 - 5757. [Abstract] [Full Text] [PDF]
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