Chapter 29 : Immune Intervention in Tuberculosis

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Regardless of the theoretical attraction of immune intervention in tuberculosis and although Bacille Calmette Guérin (BCG) provides a mainstay of global vaccination campaigns, current efforts in tuberculosis control are almost exclusively directed toward implementation of antimicrobial therapy. This chapter reviews the prospects for changing this situation by developing improved immune interventions. BCG provides some hard lessons for would-be developers of new tuberculosis vaccines. On the positive side, it vindicates the concept of vaccination as an approach to tuberculosis control. While precise numbers are hard to obtain, it seems reasonable to extrapolate that BCG has saved the lives of millions of potential victims of childhood tuberculosis. In experimental-animal models, BCG vaccination conforms to this paradigm. In naïve animals, the population of increases for several weeks after infection before being brought under the control of the immune response. Mycobacteria provide a potent signal to the innate immune system, with cell wall components triggering scavenger and Toll-like receptors on the cell surface, activating NF-κB transduction pathways leading to secretion of IL-12 and proinflammatory cytokines. If the new vaccine was to be compared to BCG, consideration would also have to be given to the question of withdrawing BCG coverage from part of the trial group, perhaps increasing their risk of potentially fatal childhood tuberculosis. The natural immune response to may well have been shaped as much by the evolutionary needs of the microbe as by those of the host.

Citation: Young D, Robertson B. 2002. Immune Intervention in Tuberculosis, p 439-451. In Kaufmann S, Sher A, Ahmed R (ed), Immunology of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817978.ch29
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1. Alderson, M. R.,, T. Bement,, C. H. Day,, L. Zhu,, D. Molesh,, Y. A. W. Skeiky,, R. Coler,, D. M. Lewinsohn,, S. G. Reed,, and D. C. Dillon. 2000. Expression cloning of an immunodominant family of Mycobacterium tuberculosis antigens using human CD4 + T cells. J. Exp. Med. 191: 551 559.
2. Altare, F.,, A. Durandy,, D. Lammas,, J. F. Emile,, S. Lamhamedi,, F. Le Deist,, P. Drysdale,, E. Jouanguy,, R. Doffinger,, F. Bernaudin,, O. Jeppsson,, J. A. Gollob,, E. Meinl,, A. W. Segal,, A. Fischer,, D. Kumararatne,, and J. L. Casanova. 1998. Impairment of mycobacterial immunity in human interleukin-12 receptor deficiency. Science 280: 1432 1435.
3. Andersen, A. B.,, and P. Brennan,. 1994. Proteins and antigens of Mycobacterium tuberculosis, p. 307 332. In B. R. Bloom (ed.), Tuberculosis: Protection, Pathogenesis, and Control. American Society for Microbiology, Washington, D.C.
4. Andersen, P. 1994. Effective vaccination of mice against Mycobacterium tuberculosis infection with a soluble mixture of secreted mycobacterial proteins. Infect. Immun. 62: 2536 2544.
5. Andersen, P.,, D. Askgaard,, A. Gottschau,, J. Bennedsen,, S. Nagai,, and I. Heron. 1992. Identification of immunodominant antigens during infection with Mycobacterium tuberculosis. Scand. J. Immunol. 36: 823 831.
6. Baldwin, S. L.,, C. D’Souza,, A. D. Roberts,, B. P. Kelly,, A. A. Frank,, M. A. Lui,, J. B. Ulmer,, K. Huygen,, D. M. McMurray,, and I. M. Orme. 1998. Evaluation of new vaccines in the mouse and guinea pig model of tuberculosis. Infect. Immun. 66: 2951 2959.
7. Bardarov, S.,, J. Kriakov,, C. Carriere,, S. Yu,, C. Vaamonde,, R. A. McAdam,, B. R. Bloom,, G. F. Hatfull,, and W. R. Jacobs, Jr. 1997. Conditionally replicating mycobacteriophages: a system for transposon delivery to Mycobacterium tuberculosis. Proc. Natl. Acad. Sci. USA 94: 10961 10966.
8. Beatty, W.,, E. Rhoades,, H.-J. Ullrich,, D. Chatterjee,, J. Heuser,, and D. Russell. 2000. Trafficking and release of mycobacterial lipids from infected macrophages. Traffic 1: 235 247.
9. Behr, M. A.,, and P. M. Small. 1997. Has BCG attenuated to impotence? Nature 389: 133 134.
10. Behr, M. A.,, M. A. Wilson,, W. P. Gill,, H. Salamon,, G. K. Schoolnik,, S. Rane,, and P. M. Small. 1999. Comparative genomics of BCG vaccines by whole-genome DNA microarray. Science 284: 1520 1523.
11. Bekker, L. G.,, P. Haslett,, G. Maartens,, L. Steyn,, and G. Kaplan. 2000. Thalidomide-induced antigen-specific immune stimulation in patients with human immunodeficiency virus type 1 and tuberculosis. J. Infect. Dis. 181: 954 965.
12. Blanchard, J. S. 1996. Molecular mechanisms of drug resistance in Mycobacterium tuberculosis. Annu. Rev. Biochem. 65: 215 239.
13. Bloom, B. R.,, and P. E. M. Fine,. 1994. The BCG experience: implications for future vaccines against tuberculosis, p. 531 558. In B. R. Bloom (ed.), Tuberculosis: Protection, Pathogenesis, and Control. American Society for Microbiology, Washington, D.C.
14. Brightbill, H. D.,, D. H. Libraty,, S. R. Krutzik,, R. B. Yang,, J. T. Belisle,, J. R. Bleharski,, M. Maitland,, M. V. Norgard,, S. E. Plevy,, S. T. Smale,, P. J. Brennan,, B. R. Bloom,, P. J. Godowski,, and R. L. Modlin. 1999. Host defense mechanisms triggered by microbial lipoproteins through toll-like receptors. Science 285: 732 736.
15. Brock, T. D. 1988. Robert Koch. A Life in Medicine and Bacteriology. Springer Velag, New York, N.Y.
16. Calmette, A. 1927. La Vaccination Preventive contra la Tuberculosis. Madison et Cie, Paris, France.
17. Chan, J.,, and S. H. E. Kaufmann,. 1994. Immune mechanisms of protection, p. 389 415. In B. R. Bloom (ed), Tuberculosis: Protection, Pathogenesis, and Control. American Society for Microbiology, Washington, D.C.
18. Chatterjee, D.,, A. D. Roberts,, K. Lowell,, P. J. Brennan,, and I. M. Orme. 1992. Structural basis of capacity of lipoarabinomannan to induce secretion of tumor necrosis factor. Infect. Immun. 60: 1249 1253.
19. Colditz, G. A.,, C. S. Berkey,, F. Mosteller,, T. F. Brewer,, M. E. Wilson,, E. Burdick,, and H. V. Fineberg. 1995. The efficacy of bacillus Calmette-Guerin vaccination of newborns and infants in the prevention of tuberculosis: meta-analyses of the published literature. Pediatrics 96: 29 35.
20. Colditz, G. A.,, T. F. Brewer,, C. S. Berkey,, M. E. Wilson,, E. Burdick,, H. V. Fineberg,, and F. Mosteller. 1994. Efficacy of BCG vaccine in the prevention of tuberculosis. Meta-analysis of the published literature. JAMA 271: 698 702.
21. Cole, S.,, R. Brosch,, J. Parkhill,, T. Garnier,, C. Churcher,, D. Harris,, S. Gordon,, K. Eiglmeier,, S. Gas,, C. E. Barry III,, F. Tekaia,, K. Badcock,, D. Basham,, D. Brown,, T. Chillingworth,, R. Connor,, R. Davies,, K. Devlin,, T. Feltwell,, S. Gentles,, N. Hamlin,, S. Holroyd,, T. Hornsby,, K. Jagels,, and B. Barrell. 1998. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 393: 537 544.
22. Comstock, G. W. 1978. Tuberculosis in twins: a reanalysis of the Prophit survey. Am. Rev. Respir. Dis. 117: 621 624.
23. Constant, P.,, F. Davodeau,, M. A. Peyrat,, Y. Poquet,, G. Puzo,, M. Bonneville,, and J. J. Fournie. 1994. Stimulation of human gamma delta T cells by nonpeptidic mycobacterial ligands. Science 264: 267 270.
24. Cooper, A. M.,, J. Magram,, J. Ferrante,, and I. M. Orme. 1997. Interleukin 12 (IL-12) is crucial to the development of protective immunity in mice intravenously infected with Mycobacterium tuberculosis. J. Exp. Med. 186: 39 45.
25. Corlan, E.,, C. Marica,, C. Macavei,, J. L. Stanford,, and C. A. Stanford. 1997. Immunotherapy with Mycobacterium vaccae in the treatment of tuberculosis in Romania. 2. Chronic or relapsed disease. Respir. Med. 91: 21 29.
26. Dannenberg, A. M.,, and G. A. W. Rook,. 1994. Pathogenesis of pulmonary tuberculosis: an interplay of tissue-damaging and macrophage-activating immune responses—dual mechanisms that control bacillary multiplication, p. 459 483. In B. R. Bloom (ed.), Tuberculosis: Protection, Pathogenesis, and Control. American Society for Microbiology, Washington, D.C.
27. Deitsch, K. W.,, E. R. Moxon,, and T. E. Wellems. 1997. Shared themes of antigenic variation and virulence in bacterial, protozoal, and fungal infections. Microbiol. Mol. Biol. Rev. 61: 281 293.
28. Deretic, V.,, and R. A. Fratti. 1999. Mycobacterium tuberculosis phagosome. Mol. Microbiol. 31: 1603 1609.
29. Dillon, D. C.,, M. R. Alderson,, C. H. Day,, D. M. Lewinsohn,, R. Coler,, T. Bement,, A. Campos-Neto,, Y. A. Skeiky,, I. M. Orme,, A. Roberts,, S. Steen,, W. Dalemans,, R. Badaro,, and S. G. Reed. 1999. Molecular characterization and human T-cell responses to a member of a novel Mycobacterium tuberculosis mtb39 gene family. Infect. Immun. 67: 2941 2950.
30. Dormandy, T. 1999. The White Death. A History of Tuberculosis. Hambledon Press, London, United Kingdom.
31. Dubos, R.,, and J. Dubos. 1952. The White Plague. Tuberculosis, Man, and Society. Rutgers University Press, New Brunswick, N.J.
32. Durban Immunotherapy Group. 1999. Immunotherapy with Mycobacterium vaccae in patients with newly diagnosed pulmonary tuberculosis: a randomised controlled trial. Lancet 354: 116119.
33. Dye, C.,, S. Scheele,, P. Dolin,, V. Pathania,, and M. C. Raviglione. 1999. Global burden of tuberculosis. Estimated incidence, prevalence, and mortality by country. JAMA 282: 677 686.
34. Fine, P. E. M. 1995. Variation in protection by BCG: implications of and for heterologous immunity. Lancet 346: 1339 1345.
35. Fine, P. E. M.,, and P. M. Small. 1999. Exogenous reinfection in tuberculosis (editorial). N. Engl. J. Med. 341: 1226 1227.
36. Flynn, J.,, J. Chan,, K. Triebold,, D. Dalton,, T. Stewart,, and B. R. Bloom. 1993. An essential role for interferon gamma in resistance to Mycobacterium tuberculosis infection. J. Exp. Med. 178: 2249 2254.
37. Flynn, J.,, M. Goldstein,, K. Triebold,, B. Koller,, and B. R. Bloom. 1992. Major histocompatibility complex class I-restricted T cells are required for resistance to Mycobacterium tuberculosis infection. Proc. Natl. Acad. Sci. USA 89: 12013 12017.
38. Gordon, S. V.,, R. Brosch,, A. Billault,, T. Garnier,, K. Eiglmeier,, and S. T. Cole. 1999. Identification of variable regions in the genomes of tubercle bacilli using bacterial artificial chromosome arrays. Mol. Microbiol. 32: 643 655.
39. Guleria, I.,, R. Teitelbaum,, R. A. McAdam,, G. Kalpana,, W. R. Jacobs, Jr.,, and B. R. Bloom. 1996. Auxotrophic vaccines for tuberculosis. Nat. Med. 2: 334 337.
40. Hess, J.,, D. Miko,, A. Catic,, V. Lehmensiek,, D. G. Russell,, and S. H. E. Kaufmann. 1998. Mycobacterium bovis Bacille Calmette-Guerin strains secreting listeriolysin of Listeria monocytogenes. Proc. Natl. Acad. Sci. USA 95: 5299 5304.
41. Heym, B.,, W. Philipp,, and S. T. Cole. 1996. Mechanisms of drug resistance in Mycobacterium tuberculosis. Curr. Top. Microbiol. Immunol. 215: 49 69.
42. Hirsch, C. S.,, Z. Toossi,, C. Othieno,, J. L. Johnson,, S. K. Schwander,, S. Robertson,, R. S. Wallis,, K. Edmonds,, A. Okwera,, R. Mugerwa,, P. Peters,, and J. J. Ellner. 1999a. Depressed T-cell interferon-gamma responses in pulmonary tuberculosis: analysis of underlying mechanisms and modulation with therapy. J. Infect. Dis. 180: 2069 2073.
43. Hirsch, C. S.,, Z. Toossi,, G. Vanham,, J. L. Johnson,, P. Peters,, A. Okwera,, R. Mugerwa,, P. Mugyenyi,, and J. J. Ellner. 1999b. Apoptosis and T cell hyporesponsiveness in pulmonary tuberculosis. J. Infect. Dis. 179: 945 953.
44. Hmama, Z.,, R. Gabathuler,, W. A. Jefferies,, G. de Jong,, and N. E. Reiner. 1998. Attenuation of HLA-DR expression by mononuclear phagocytes infected with Mycobacterium tuberculosis is related to intracellular sequestration of immature class II heterodimers. J. Immunol. 161: 4882 4893.
45. Höner Zu Bentrup, K.,, A. Miczak,, D. L. Swenson,, and D. G. Russell. 1999. Characterization of activity and expression of isocitrate lyase in Mycobacterium avium and Mycobacterium tuberculosis. J. Bacteriol. 181: 7161 7167.
46. Hopewell, P. C. 1992. Impact of human immunodeficiency virus infection on the epidemiology, clinical features, management and control of tuberculosis. Clin. Infect. Dis. 18: 540 546.
47. Horwitz, M. A.,, B. W. Lee,, B. J. Dillon,, and G. Harth. 1995. Protective immunity against tuberculosis induced by vaccination with major extracellular proteins of Mycobacterium tuberculosis. Proc. Natl. Acad. Sci. USA 92: 1530 1534.
48. Huygen, K.,, J. Content,, O. Denis,, D. L. Montgomery,, A. M. Yawman,, R. R. Deck,, C. M. DeWitt,, I. M. Orme,, S. Baldwin,, C. D’Souza,, A. Drowart,, E. Lozes,, P. Vandenbussche,, J. P. Van Vooren,, M. A. Liu,, and J. B. Ulmer. 1996. Immunogenicity and protective efficacy of a tuberculosis DNA vaccine. Nat. Med. 2: 893 898.
49. Johnson, B. J.,, L. G. Bekker,, R. Rickman,, S. Brown,, M. Lesser,, S. Ress,, P. Willcox,, L. Steyn,, and G. Kaplan. 1997. rhuIL-2 adjunctive therapy in multidrug resistant tuberculosis: a comparison of two treatment regimens and placebo. Tubercle Lung Dis. 78: 195 203.
50. Johnson, J. L.,, R. M. Kamya,, A. Okwera,, A. M. Loughlin,, S. Nyole,, D. L. Hom,, R. S. Wallis,, C. S. Hirsch,, K. Wolski,, J. Foulds,, R. D. Mugerwa,, and J. J. Ellner. 2000. Randomized controlled trial of Mycobacterium vaccae immunotherapy in non-human immunodeficiency virus-infected Ugandan adults with newly diagnosed pulmonary tuberculosis. The Uganda- Case Western Reserve University Research Collaboration. J. Infect. Dis. 181: 1304 1312.
51. Jouanguy, E.,, F. Altare,, S. Lamhamedi,, P. Revy,, J. F. Emile,, M. Newport,, M. Levin,, S. Blanche,, E. Seboun,, A. Fischer,, and J. L. Casanova. 1996. Interferon-gamma-receptor deficiency in an infant with fatal bacille Calmette-Guerin infection. N. Engl. J. Med. 335: 1956 1961.
52. Jungblut, P. R.,, U. E. Schaible,, H. J. Mollenkopf,, U. Zimny Arndt,, B. Raupach,, J. Mattow,, P. Halada,, S. Lamer,, K. Hagens,, and S. H. E. Kaufmann. 1999. Comparative proteome analysis of Mycobacterium tuberculosis and Mycobacterium bovis BCG strains: towards functional genomics of microbial pathogens. Mol. Microbiol. 33: 1103 1117.
53. Karonga Prevention Trial Group. 1996. Randomised controlled trial of single BCG, repeated BCG, or combined BCG and killed Mycobacterium leprae vaccine for prevention of leprosy and tuberculosis in Malawi. Lancet 348: 1724.
54. Kaufmann, S. H. E. 1988. CD8 + T lymphocytes in intracellular microbial infections. Immunol. Today 9: 168 174.
55. Koch, R. 1882. Die aetiologie der Tuberculose. Berl. Klin. Wochenschr. 19: 221 230.
56. Kochi, A. 1991. The global tuberculosis situation and the new control strategy of the World Health Organization. Tubercle 72: 1 6.
57. Lowrie, D. B.,, R. E. Tascon,, V. L. D. Bonato,, V. M. F. Lima,, L. H. Faccioli,, E. Stavropoulos,, M. J. Colston,, R. G. Hewinson,, K. Moelling,, and C. L. Silva. 1999. Therapy of tuberculosis in mice by DNA vaccination. Nature 400: 269 271.
58. Mahairas, G. G.,, P. J. Sabo,, M. J. Hickey,, D. C. Singh,, and C. K. Stover. 1996. Molecular analysis of genetic differences between Mycobacterium bovis BCG and virulent M. bovis. J. Bacteriol. 178: 1274 1282.
59. Mazzaccaro, R.,, M. Gedde,, E. Jensen,, H. van Santen,, H. Ploegh,, K. Rock,, and B. R. Bloom. 1996. Major histocompatibility class I presentation of soluble antigen facilitated by Mycobacterium tuberculosis infection. Proc. Natl. Acad. Sci. USA 93: 11786 11791.
60. McCune, R. M.,, F. M. Feldman,, H. P. Lambert,, and W. Mc- Dermott. 1966. Microbial persistence. I. The capacity of tubercle bacilli top survive sterilization in mouse tissues. J. Exp. Med. 123: 445 468.
61. McLean, A., 1999. Development and use of vaccines against evolving pathogens: vaccine design, p. 138 151. In S. C. Stearns (ed.), Evolution in Health and Disease. Oxford University Press, Oxford, United Kingdom.
62. McMurray, D. N., 1994. Guinea pig model of tuberculosis, p. 135 148. In B. R. Bloom (ed.), Tuberculosis: Protection, Pathogenesis, and Control. American Society for Microbiology, Washington, D.C.
63. Means, T. K.,, S. Wang,, E. Lien,, A. Yoshimura,, D. T. Golenbock,, and M. J. Fenton. 1999. Human Toll-like receptors mediate cellular activation by Mycobacterium tuberculosis. J. Immunol. 163: 3920 3927.
64. Moody, D. B.,, B. B. Reinhold,, M. R. Guy,, E. M. Beckman,, D. E. Frederique,, S. T. Furlong,, S. Ye,, V. N. Reinhold,, P. A. Sieling,, R. L. Modlin,, G. S. Besra,, and S. A. Porcelli. 1997. Structural requirements for glycolipid antigen recognition by CD1brestricted T cells. Science 278: 283 286.
65. Moreira, A. L.,, E. P. Sampaio,, A. Zmuidzinas,, P. Frindt,, K. A. Smith,, and G. Kaplan. 1993. Thalidomide exerts its inhibitory action on tumor necrosis factor alpha by enhancing mRNA degradation. J. Exp. Med. 177: 1675 1680.
66. Musser, J. M.,, A. Amin,, and S. Ramaswamy. 2000. Negligible genetic diversity of Mycobacterium tuberculosis host immune system targets: evidence of limited selective pressure. Genetics 155: 7 16.
67. Newport, M. J.,, C. M. Huxley,, S. Huston,, C. M. Hawrylowicz,, B. A. Oostra,, R. Williamson,, and M. Levin. 1996. A mutation in the interferon-gamma-receptor gene and susceptibility to mycobacterial infection. N. Engl. J. Med. 335: 1941 1949.
68. Ogg, G. S.,, and A. J. McMichael. 1998. HLA-peptide tetrameric complexes. Curr. Opin. Immunol. 10: 393 396.
69. Onyebujoh, P. C.,, T. Abdulmumini,, S. Robinson,, G. A. Rook,, and J. L. Stanford. 1995. Immunotherapy with Mycobacterium vaccae as an addition to chemotherapy for the treatment of pulmonary tuberculosis under difficult conditions in Africa. Respir. Med. 89: 199 207.
70. Orme, I. M.,, and F. M. Collins,. 1994. Mouse model of tuberculosis, p. 113 134. In B. R. Bloom (ed.), Tuberculosis: Protection, Pathogenesis, and Control. American Society for Microbiology, Washington, D.C.
71. Pablos-Mendez, A.,, M. Raviglione,, A. Laszlo,, N. Binkin,, H. Rieder,, F. Bustreo,, D. Cohn,, C. Lambregts-van Weezenbeek,, S. Kim,, P. Chaulet,, and P. Nunn. 1998. Global surveillance for antituberculosis-drug resistance, 1994 1997. World Health Organization—International Union against Tuberculosis and Lung Disease Working Group on Anti-Tuberculosis Drug Resistance Surveillance. N. Engl. J. Med. 338: 1641 1649.
72. Palmer, C. E.,, and M. W. Long. 1966. Effects of infection with atypical mycobacteria on BCG vaccination and tuberculosis. Am. Rev. Respir. Dis. 94: 553 568.
73. Pancholi, P.,, A. Mirza,, N. Bhardwaj,, and R. M. Steinman. 1993. Sequestration from immune CD4 + T cells of mycobacteria growing in human macrophages. Science 260: 984 986.
74. Pelicic, V.,, M. Jackson,, J. M. Reyrat,, W. R. Jacobs, Jr.,, B. Gicquel,, and C. Guilhot. 1997. Efficient allelic exchange and transposon mutagenesis in Mycobacterium tuberculosis. Proc. Natl. Acad. Sci. USA 94: 10955 10960.
75. Ramakrishnan, L.,, N. A. Federspiel,, and S. Falkow. 2000. Granuloma-specific expression of mycobacterium virulence proteins from the glycine-rich PE-PGRS family. Science 288: 1436 1439.
76. Roache, T. I.,, C. H. Barton,, D. Chatterjee,, and J. M. Blackwell. 1993. Macrophage activation: lipoarabinomannan from avirulent and virulent strains of Mycobacterium tuberculosis differentially induces the early genes c-fos, KC, JE, and tumour necrosis factor-alpha. J. Immunol. 150: 1886 1896.
77. Robertson, B. D.,, and T. F. Meyer. 1992. Genetic variation in pathogenic bacteria. Trends Genet. 8: 422 427.
78. Rook, G. A.,, and R. Hernandez-Pando. 1996. The pathogenesis of tuberculosis. Annu. Rev. Microbiol. 50: 259 284.
79. Schaible, U. E.,, K. Hagens,, K. Fischer,, H. L. Collins,, and S. H. E. Kaufmann. 2000. Intersection of group 1 CD1 molecules and mycobacteria in different intracellular compartments of dendritic cells. J. Immunol. 164: 4843 4852.
80. Sieling, P. A.,, D. Chatterjee,, S. A. Porcelli,, T. I. Prigozy,, R. J. Mazzaccaro,, T. Soriano,, B. R. Bloom,, M. B. Brenner,, M. Kronenberg,, P. J. Brennan,, and R. L. Modlin. 1995. CD1-restricted T cell recognition of microbial lipoglycan antigens. Science 269: 227 230.
81. Snewin, V.,, G. Stewart,, and D. Young,. 2000. Genetic strategies for vaccine development, p. 279 296. In G. F. Hatfull, and W. R. Jacobs, Jr. (ed.), Molecular Genetics of Mycobacteria. American Society for Microbiology, Washington, D.C.
82. Sorensen, A. L.,, S. Nagai,, G. Houen,, P. Andersen,, and A. B. Andersen. 1995. Purification and characterization of a low-molecular- mass T-cell antigen secreted by Mycobacterium tuberculosis. Infect. Immun. 63: 1710 1717.
83. Sousa, A. O.,, R. J. Mazzaccaro,, R. G. Russell,, F. K. Lee,, O. C. Turner,, S. Hong,, L. Van Kaer,, and B. R. Bloom. 2000. Relative contributions of distinct MHC class I-dependent cell populations in protection to tuberculosis infection in mice. Proc. Natl. Acad. Sci. USA 97: 4204 4208.
84. Sreevatsan, S.,, X. Pan,, K. E. Stockbauer,, N. D. Connell,, B. N. Kreiswirth,, T. S. Whittam,, and J. M. Musser. 1997. Restricted structural gene polymorphism in the Mycobacterium tuberculosis complex indicates evolutionarily recent global dissemination. Proc. Natl. Acad. Sci. USA 94: 9869 9874.
85. Stanford, J. L.,, G. A. Rook,, G. M. Bahr,, Y. Dowlati,, R. Ganapati,, K. Ghazi Saidi,, S. Lucas,, G. Ramu,, P. Torres,, H. Minh Ly,, and N. Anstey. 1990. Mycobacterium vaccae in immunoprophylaxis and immunotherapy of leprosy and tuberculosis. Vaccine 8: 525 530.
86. Stenger, S.,, R. J. Mazzaccaro,, K. Uyemura,, S. Cho,, P. F. Barnes,, J. P. Rosat,, A. Sette,, M. B. Brenner,, S. A. Porcelli,, B. R. Bloom,, and R. L. Modlin. 1997. Differential effects of cytolytic T cell subsets on intracellular infection. Science 276: 1684 1687.
87. Sugita, M.,, E. P. Grant,, E. van Donselaar,, V. W. Hsu,, R. A. Rogers,, P. J. Peters,, and M. B. Brenner. 1999. Separate pathways for antigen presentation by CD1 molecules. Immunity 11: 743 752.
88. Tascon, R. E.,, M. J. Colston,, S. Ragno,, E. Stavropoulos,, D. Gregory,, and D. B. Lowrie. 1996. Vaccination against tuberculosis by DNA injection. Nat. Med. 2: 888 892.
89. Tascon, R. E.,, E. Stavropoulos,, K. V. Lukacs,, and M. J. Colston. 1998. Protection against Mycobacterium tuberculosis infection by CD8 + T cells requires the production of gamma interferon. Infect. Immun. 66: 830 834.
90. Teitelbaum, R.,, M. Cammer,, M. L. Maitland,, N. E. Freitag,, J. Condeelis,, and B. R. Bloom. 1999. Mycobacterial infection of macrophages results in membrane-permeable phagosomes. Proc. Natl. Acad. Sci. USA 96: 15190 15195.
91. Teitelbaum, R.,, A. Glatman-Freedman,, B. Chen,, J. B. Robbins,, E. Unanue,, A. Casadevall,, and B. R. Bloom. 1998. A mAb recognizing a surface antigen of Mycobacterium tuberculosis en hances host survival. Proc. Natl. Acad. Sci. USA 95: 15688 15693.
92. Tramontana, J. M.,, U. Utaipat,, A. Molloy,, P. Akarasewi,, M. Burroughs,, S. Makonkawkeyoon,, B. Johnson,, J. D. Klausner,, W. Rom,, and G. Kaplan. 1995. Thalidomide treatment reduces tumor necrosis factor alpha production and enhances weight gain in patients with pulmonary tuberculosis. Mol. Med. 1: 384 397.
93. Turner, O. C.,, A. D. Roberts,, A. A. Frank,, S. W. Phalen,, D. M. McMurray,, J. Content,, O. Denis,, S. D’Souza,, A. Tanghe,, K. Huygen,, and I. M. Orme. 2000. Lack of protection in mice and necrotizing pneumonia with bronchiolitis in guinea pigs immunized with vaccines directed against the hsp60 molecule of Mycobacterium tuberculosis. Infect. Immun. 68: 3674 3679.
94. Wallace, J. G. 1961. The heat resistance of tubercle in the lungs of infected mice. Am. Rev. Respir. Dis. 83: 866 871.
95. Watts, C. 1997. Capture and processing of exogenous antigens for presentation on MHC molecules. Annu. Rev. Immunol. 15: 821 850.
96. Wilson, M.,, J. DeRisi,, H. H. Kristensen,, P. Imboden,, S. Rane,, P. O. Brown,, and G. K. Schoolnik. 1999. Exploring drug-induced alterations in gene expression in Mycobacterium tuberculosis by microarray hybridization. Proc. Natl. Acad. Sci. USA 96: 12833 12838.

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