Chapter 7 : Human Tuberculosis

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Human Tuberculosis, Page 1 of 2

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The study of human mycobacterial granuloma is rendered difficult by the limitations of tissue availability and because direct study of protective immune response to is impossible. Bronchoalveolar lavage (BAL) can be used to assess localized lung immune responses during tuberculosis (TB), provides insights into immunologicc ompartmentalization, and may reflect processes in the granulomatous tissue adjacent to the bronchoalveolar spaces. The study of bronchoalveolar cells (BAC) from the bronchoalveolar spaces also allows assessment of alveolar MΦ and lymphocyte functions at the site of disease in the lungs from TB patients. Researchers have recently studied BAC from tuberculin skin test (TST)-positive healthy household contact (HHC) of sputum culture-positive, untreated TB index cases with three-plus-positive sputum smears, i.e., highly infectious cases. Ex vivo studies of cells from the bronchoalveolar spaces have been performed to feasibly obtain cells from the site of infection (reactivation disease) during TB. The most prominent finding of BAL studies in TB patients is a compartmentalized pulmonary immune response. Characterization of alveolar lymphocytes in human pulmonary tuberculosis are provided in this chapter. Understanding of the role of dendritic cells (DC) during mycobacterial infection is emerging. In vitro data indicate that DC are potent antigen-presenting cells as well as activators of T cells. Resolution of granuloma formation after successful TB chemotherapy is evidence for the importance of metabolically active in triggering granulomatous tissue reactions.

Citation: Schwander S, Ellner J. 2003. Human Tuberculosis, p 173-206. In Boros D (ed), Granulomatous Infections and Inflammations. ASM Press, Washington, DC. doi: 10.1128/9781555817879.ch7

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Figure 1

Frequencies of IFN-γ-producing cells in PBMC and BAC of tuberculin skin testpositive healthy household contacts of patients with active tuberculosis (HHC) and healthy tuberculin skin test-positive control individuals from the community (CC) by ELISPOT assay. Frequencies of IFN-γ-producing cells in PBMC and BAC from HHC ( = 10) (A) and CC ( = 15) (B) were determined by ELISPOT assay and are expressed as IFN-γ spots per 10 PBMC and BAC. PBMC and BAC were stimulated with PPD and Ag 85 complex from H37Rv culture filtrate (Ag 85co). Control cultures (background) were stimulated with medium alone (Medium). Results are presented as pairs of autologous PBMC and BAC data for each study individual. Visibility of overlapping data points was improved by separating the data points through minor horizontal shifting. •, HHC and CC individuals in whom frequencies of IFN-γ-producing cells in BAC were ≥ 3-fold higher than those in PBMC (for HHC, = 4 for PPD and = 5 for Ag 85co; for CC, = 1 for PPD and = 1 for Ag 85co). Frequencies of IFN-γ-producing BAC in response to Ag 85co were significantly higher in BAC from HHC (A) than in BAC from CC (B) ( = 0.022). Reprinted from reference 116 with permission. © 2000 The American Association of Immunologists, Inc.

Citation: Schwander S, Ellner J. 2003. Human Tuberculosis, p 173-206. In Boros D (ed), Granulomatous Infections and Inflammations. ASM Press, Washington, DC. doi: 10.1128/9781555817879.ch7
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Figure 2

Cytospin preparations of BAC (original magnification, ×160). Wright's stain of BAC from unaffected (A) and affected (B) lung of pulmonary tuberculosis patient shows increase in alveolar lymphocytes in affected lung (arrow); an occasional neutrophil also can be seen. Reprinted from reference 115 with permission of the University of Chicago Press. © 1996 by The University of Chicago. All rights reserved.

Citation: Schwander S, Ellner J. 2003. Human Tuberculosis, p 173-206. In Boros D (ed), Granulomatous Infections and Inflammations. ASM Press, Washington, DC. doi: 10.1128/9781555817879.ch7
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Figure 3

DNA synthesis by BAC (A) and PBMC (B) to mycobacterial and nonmycobacterial antigens from patients with pulmonary tuberculosis and healthy subjects. BAC and PBMC were stimulated with tetanus toxoid (TT), antigen, 30/32-kDa antigen 85-protein complex from H37Rv culture filtrate (Ag 85), or PPD, and incorporation of [3H]thymidine was determined after 5 days in culture. Responses of unstimulated cells (culture medium) were <1,000 cpm (data not shown). Horizontal lines represent medians. For PPD, = 16 tuberculosis patients and = 23 healthy subjects; for other stimuli, > 5 (both study groups). Reprinted from reference 117 with permission of the University of Chicago Press. © 1998 by the Infectious Diseases Society of America. All rights reserved.

Citation: Schwander S, Ellner J. 2003. Human Tuberculosis, p 173-206. In Boros D (ed), Granulomatous Infections and Inflammations. ASM Press, Washington, DC. doi: 10.1128/9781555817879.ch7
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Figure 4

Frequencies of IFN-γ-producing BAC by ELISPOT from patients with pulmonary tuberculosis and healthy subjects, determined in cells stimulated with medium alone (both healthy subjects and tuberculosis patients) or with PPD (healthy subjects [=4], radiographically unaffected lungs from tuberculosis patients [ = 3; two symbols overlap], and radiographically affected lungs from tuberculosis patients [ = 6]). Horizontal lines represent medians. Reprinted from reference 117 with permission of the University of Chicago Press. © 1998 by the Infectious Diseases Society of America. All rights reserved.

Citation: Schwander S, Ellner J. 2003. Human Tuberculosis, p 173-206. In Boros D (ed), Granulomatous Infections and Inflammations. ASM Press, Washington, DC. doi: 10.1128/9781555817879.ch7
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1. Adams, D. O. 1976. The granulomatous inflammatory response. Am. J. Pathol. 84:164191.
2. Agostini, C.,, A. Perin,, and M. D. Semenzato. 1998. Cell apoptosis and granulomatous lung diseases. Curr. Opin. Pulm. Med. 4:261266.
3. Ainslie, G. M.,, J. A. Solomon,, and E. D. Bateman. 1992. Lymphocyte and lymphocyte subset numbers in blood and in bronchoalveolar lavage and pleural fluid in various forms of human pulmonary tuberculosis at presentation and during recovery. Thorax 47:513518.
4. Aoki, Y.,, O. Katoh,, Y. Nakanishi,, S. Kuroki,, and H. Yamada. 1994. A comparison study of IFN-γ, ADA, and CA 125 as the diagnosticparameters in tuberculous pleuritis. Respir. Med. 88:139143.
5. Aubert-Pivert, E. M.,, F. M. Chedevergne,, G. M. Lopez-Ramirez,, J. H. Colle,, P. L. Scheinmann,, B. M. Gicquel,, and J. M. de Blic. 2000. Cytokine transcripts in pediatric tuberculosis: a study with bronchoalveolar cells. Tuber. Lung Dis. 80:249258.
6. Aung, H.,, Z. Toossi,, S. M. McKenna,, P. Gogate,, J. Sierra,, E. Sada,, and E. A. Rich. 2000. Expression of transforming growth factor-β but not tumor necrosis factor-α, interferon- γ, and interleukin-4 in granulomatous lung lesions in tuberculosis. Tuber. Lung Dis. 80:6167.
7. Balaji, K. N.,, S. K. Schwander,, E. A. Rich,, and W. H. Boom. 1995. Alveolar macrophages as accessory cells for human gamma delta T cells activated by Mycobacterium tuberculosis. J. Immunol. 154:59595968.
8. Barnes, P. F.,, S. Lu,, J. S. Abrams,, E. Wang,, M. Yamamura,, and R. L. Modlin. 1993. Cytokine production at the site of disease in human tuberculosis. Infect. Immun. 61: 34823489.
9. Barnes, P. F.,, S. D. Mistry,, C. L. Cooper,, C. Pirmez,, T. H. Rea,, and R. L. Modlin. 1989. Compartmentalization of a CD4+ T lymphocyte subpopulation in tuberculous pleuritis. J. Immunol. 142:11141119.
10. Barnes, P. F.,, S. J. Fong,, P. J. Brennan,, P. E. Twomey,, A. Mazumder,, and R. L. Modlin. 1990. Local production of tumor necrosis factor and IFN-γin tuberculous pleuritis. J. Immunol. 145:149154.
11. Bates, J. H. 1980. Transmission and pathogenesis of tuberculosis. Clin. Chest Med. 1: 167174.
12. Baughman R. P.,, M. N. Dohn,, R. G. Loudon,, and P. T. Frame. 1991. Bronchoscopy with bronchoalveolar lavage in tuberculosis and fungal infections. Chest 99:9297.
13. Beckman, E. M.,, S. A. Porcelli,, C. T. Morita,, S. M. Behar,, S. T. Furlong,, and M. B. Brenner. 1994. Recognition of a lipid antigen by CD1-restricted αβ+ T cells. Nature 372: 691694.
14. Bergeron, A.,, M. Bonay,, M. Kambouchner,, D. Lecossier,, M. Riquet,, P. Soler,, A. Hance,, and A. Tazi. 1997. Cytokine patterns in tuberculosis and sarcoid granulomas. Correlations with histopathologicfeatures of the granulomatous response. J. Immunol. 159: 30343043.
15. Berman, J. S.,, R. L. Blumenthal,, H. Kornfeld,, J. A. Cook,, W. W. Cruikshank,, M. W. Vermeulen,, D. Chatterjee,, J. T. Belisle,, and M. J. Fenton. 1996. Chemotactic activity of mycobacterial lipoarabinomannans for human blood T lymphocytes in vitro. J. Immunol. 156:38283835.
16. Bermudez, L. E.,, and J. Goodman. 1996. Mycobacterium tuberculosis invades and replicates within type II alveolar cells. Infect. Immun. 64:14001406.
17. Bermudez, L. E.,, F. J. Sangari,, P. Kolonoski,, M. Petrofsky,, and J. Goodman. 2002. The efficiency of the translocation of Mycobacterium tuberculosis across a bilayer of epithelial and endothelial cells as a model of the alveolar wall is a consequence of transport within mononuclear phagocytes and invasion of alveolar epithelial cells. Infect. Immun. 70:140146.
18. Boom, W. H. 1996. The role of T cell subsets in Mycobacterium tuberculosis infection. Infect. Agents Dis. 5:7381.
19. Boussiotis, V. A.,, E. T. Tsai,, E. J. Yunis,, S. Thim,, J. C. Delgado,, C. C. Dascher,, A. Berezovskaya,, D. Rousset,, J.-M. Reynes,, and A. E. Goldfeld. 2000. IL-10 producing T cells suppress immune responses in anergic tuberculosis patients. J. Clin. Invest. 105: 13171325.
20. Braun, M. M.,, N. Badi,, R. W. Ryder,, E. Baende,, Y. Mukadi,, M. Nsuami,, B. Matela,, J. C. Williame,, M. Kaboto,, and W. Heyward. 1991. A retrospective study of the risk of tuberculosis among women of childbearing age in Zaire. Am. Rev. Respir. Dis. 143: 10551064.
21. Canetti, G. 1955. The Tubercle Bacillus in the Pulmonary Lesion of Man. Histobacteriology and Its Bearing on the Therapy of Pulmonary Tuberculosis. Springer Publishing Company, Inc., New York, N.Y.
22. Choi, H.-S.,, P. R. Rai,, H. W. Chu,, C. Cool,, and E. D. Chan. 2002. Analysis of nitric oxide synthase and nitrotyrosine expression in human pulmonary tuberculosis. Am. J. Respir. Crit. Care Med. 166:178186.
23. Daley, C. L.,, P. M. Small,, G. F. Schecter,, G. K. Schoolnik,, R. A. McAdam,, W. R. Jacobs, Jr.,, and P. C. Hopewell. 1992. An outbreak of tuberculosis with accelerated progression among persons infected with the human immunodeficiency virus. An analysis using restriction-fragment-length polymorphisms. N. Engl. J. Med. 326:231235.
24. Dhand, R.,, A. De,, N. K. Ganguly,, N. Gupta,, S. Jaswal,, S. K. Malik,, and K. K. Kohli. 1988. Factors influencing the cellular response in bronchoalveolar lavage and peripheral blood of patients with pulmonary tuberculosis. Tubercle 69:161173.
25. Dhand, R.,, N. K. Ganguly,, N. Dang,, M. Goyal,, and S. Jaswal. 1990. Effect of chemotherapy on cell counts in peripheral blood and bronchoalveolar lavage of patients with pulmonary tuberculosis. Indian J. Med. Res. 91:419424.
26. Di Perri, G.,, A. Cazzadori,, S. Vento,, S. Bonora,, M. Malena,, L. Bontempini,, M. Lanzafame,, B. Allegranzi,, and E. Concia. 1996. Comparative histopathological study of pulmonary tuberculosis in human immunodeficiency virus-infected and non-infected patients. Tuber. Lung Dis. 77:244249.
27. Di Perri, G.,, M. Cruciani,, M. C. Danzi,, R. Luzzati,, G. De Checchi,, M. Malena,, S. Pizzighella,, R. Mazzi,, M. Solbiati,, E. Concia,, and D. Bassetti. 1989. Nosocomial epidemic of active tuberculosis among HIV-infected patients. Lancet 30:15021504.
28. Diamond, G.,, D. Legarda,, and L. K. Ryan. 2000. The innate immune response of the respiratory epithelium. Immunol. Rev. 173:2738.
29. Diamond, G.,, V. Kaiser,, J. Rhodes,, J. P. Russell,, and C. L. Bevins. 2000. Transcriptional regulation of β-defensin gene expression in tracheal epithelial cells. Infect. Immun. 68: 113119.
30. Dlugovitzky, D.,, A. Torres-Morales,, L. Rateni,, M. A. Farroni,, C. Largacha,, O. Molteni,, and O. Bottasso. 1997. Circulating profile of Th1 and Th2 cytokines in tuberculosis patients with different degrees of pulmonary involvement. FEMS Immunol. Med. Microbiol. 18:203207.
31. Doenhoff, M. J. 1997. A role for granulomatous inflammation in the transmission of infectious disease: schistosomiasis and tuberculosis. Parasitology 115:S113S125.
32. Doenhoff, M. J. 1998. Granulomatous inflammation and the transmission of infection: schistosomiasis—and TB too? Immunol. Today 19:462467.
33. Dye, C.,, S. Scheele,, P. Dolibn,, V. Pathania,, and M. C. Raviglione. 1999. Consensus statement. Global burden of tuberculosis: estimated incidence, prevalence, and mortality by country. WHO global Surveillance and Monitoring Project. JAMA 282:677686.
34. Ellner, J. J. 1978. Pleural fluid and peripheral blood lymphocyte function in tuberculosis. Ann. Intern. Med. 89:932933.
35. Ellner, J. J. 1978. Suppressor adherent cells in human tuberculosis. J. Immunol. 121: 25732579.
36. Ellner, J. J. 1997. Regulation of the human immune response during tuberculosis. J. Lab. Clin. Med. 130:469475.
37. Ellner, J. J.,, P. F. Barnes,, and R. L. Modlin. 1988. The immunology of tuberculous pleurisy. Semin. Respir. Infect. 3:335342.
38. Faith, A.,, D. M. Schellenberg,, A. D. M. Rees,, and D. M. Mitchell. 1992. Antigenic specificity and subset analysis of T cells isolated from the bronchoalveolar lavage and pleural effusion of patients with lung disease. Clin. Exp. Immunol. 87:272278.
39. Falcao, R. P.,, and C. Bottura. 1981. A comparative study of lymphocytes in effusions of patients with tuberculosis or malignant disease. Clin. Exp. Immunol. 45:201204.
40. Farer, L. S.,, A. M. Lowell,, and M. P. Meador. 1979. Extrapulmonary tuberculosis in the United States. Am. J. Epidemiol. 109:205217.
41. Fenhalls, G.,, A. Wong,, J. Bezuidenhout,, P. van Helden,, P. Bardin,, and P. T. Lukey. 2000. In situ production of gamma interferon, interleukin-4, and tumor necrosis factor alpha mRNA in human lung tuberculous granulomas. Infect. Immun. 68:28272836.
42. Fenton, M. J.,, M. W. Vermeulen,, S. Kim,, M. Burdick,, R.M. Strieter,, and H. Kornfeld. 1997. Induction of gamma interferon production in human alveolar macrophages by Mycobacterium tuberculosis. Infect. Immun. 65:51495156.
43. Ferguson, J. S.,, D. R. Voelker,, J. A. Ufnar,, A. J. Dawson,, and L. S. Schlesinger. 2002. Surfactant protein D inhibition of human macrophage uptake of Mycobacterium tuberculosis is independent of bacterial agglutination. J. Immunol. 168:13091314.
44. Ferguson, J. S.,, D. R. Voelker,, F. X. McCormack,, and L. S. Schlesinger. 1999. Surfactant protein D binds to Mycobacterium tuberculosis bacilli and lipoarabinomannan via carbohydrate- lectin interactions resulting in reduced phagocytosis of the bacteria by macrophages. J. Immunol. 163:312321.
45. Flynn, J. L.,, M. M. Goldstein,, J. Chan,, K. J. Triebold,, K. Pfeffer,, C. J. Lowenstein,, R. Schreiber,, T. W. Mak,, and B. R. Bloom. 1995. Tumor necrosis factor-α is required in the protective immune response against mycobacterium tuberculosis in mice. Immunity 2:561572.
46. Förtsch, D.,, M. Röllinghoff,, and S. Stenger. 2000. IL-10 converts human dendritic cells into macrophage-like cells with increased antibacterial activity against virulent Mycobacterium tuberculosis. J. Immunol. 165:978987.
47. Fujiwara, H.,, and I. Tsuyuguchi. 1986. Frequency of tuberculin-reactive T-lymphocytes in pleural fluid and blood from patients with tuberculous pleuritis. Chest 89:530532.
48. Fujiwara, H.,, M. E. Kleinhenz,, R. S. Wallis,, and J. J. Ellner. 1986. Increased interleukin- 1 production and monocyte suppressor cell activity associated with human tuberculosis. Am. Rev. Respir. Dis. 133:7377.
49. Fujiwara, H.,, Y. Okuda,, T. Fukukawa,, and I. Tsuyuguchi. 1982. In vitro tuberculin reactivity of lymphocytes from patients with tuberculous pleurisy. Infect. Immun. 35: 402409.
50. Gambon-Deza, F.,, M. Pacheco Carracedo,, T. Cerda Mota,, and J. Montes Santiago. 1995. Lymphocyte populations during tuberculosis infection: Vβ repertoires. Infect. Immun. 63:12351240.
51. Gasser, A.,, and J. Möst. 1999. Generation of multinucleated giant cells in vitro by culture of human monocytes with Mycobacterium bovis BCG in combination with cytokinecontaining supernatants. Infect. Immun. 67:395402.
52. Gaynor, C. D.,, F. X. McCormack,, D. R. Voelcker,, S. E. McGowan,, and S. L. Schlesinger. 1995. Pulmonary surfactant protein A mediates enhanced phagocytosis of Mycobacterium tuberculosis by a direct interaction with human macrophages. J. Immunol. 155: 53435351.
53. Giacomini, E.,, E. Iona,, L. Ferroni,, M. Miettinen,, L. Fattorini,, G. Orefici,, I. Julkunen,, and E. M. Coccia. 2001. Infection of human macrophages and dendritic cells with Mycobacterium tuberculosis induces a differential cytokine gene expression that modulates T cell response. J. Immunol. 166:70337041.
54. Gilks, C. F.,, R. J. Brindle,, L. S. Otieno,, S. M. Bhatt,, R. S. Newnham,, P. M. Simani,, G. N. Lule,, G. B. A. Okelo,, W. M. Watkins,, P. G. Waiyaki,, J. O. B. Were,, and D. A. Warell. 1990. Extrapulmonary and disseminated tuberculosis in HIV-1-seropositive patients presenting to the acute medical services in Nairobi. AIDS 4:981985.
55. Gryzbowski, S.,, G. D. Barnett,, and K. Styblo. 1975. Contacts of cases of active tuberculosis. Bull. Int. Union Tuberc. 50:90106.
56. Gursel, G.,, N. Gokcora,, S. Elbeg,, B. Samurkasoglu,, and N. Ekim. 1995. Tumor necrosis factor-α (TNF-α) in pleural fluids. Tuber. Lung Dis. 76:370371.
57. Harf, R.,, Y. Frobert,, N. Biot,, C. Lancestre,, C. Ollagnier,, and M. Perin-Fayolle. 1985. Donnees du lavage broncho-alveolaire dans la tuberculose pulmonaire localisee. Rev. Pneumol. Clin. 41:101105.
58. Henderson, R. A.,, S. C. Watkins,, and J. L. Flynn. 1997. Activation of human dendritic cells following infection with Mycobacterium tuberculosis. J. Immunol. 159:635643.
59. 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. 1999. Depressed T-cell interferon-gamma responses in pulmonary tuberculosis: analysis of underlying mechanisms and modulation with therapy. J. Infect. Dis. 180:20692073.
60. Hirsch, C. S.,, J. J. Ellner,, D. G. Russell,, and E. A. Rich. 1994. Complement receptormediated uptake and tumor necrosis factor-alpha-mediated growth inhibition of Mycobacterium tuberculosis by human alveolar macrophages. J. Immunol. 152:743753.
61. Hirsch, C. S.,, R. Hussain,, Z. Toossi,, G. Dawood,, F. Shahid,, and J. J. Ellner. 1996. Cross-modulation by transforming growth factor β in human tuberculosis: suppression of antigen-driven blastogenesis and interferon γ production. Proc. Natl. Acad. Sci. USA 93:31933198.
62. Hirsch, C. S.,, Z. Toossi,, G. Vanham,, J. L. Johnson,, P. Peters,, A. Okwera,, R. Mugerwa,, P. Mugyenyi,, and J. J. Ellner. 1999. Apoptosis and T cell hyporesponsiveness in pulmonary tuberculosis. J. Infect. Dis. 179:945953.
63. Hirsch, C. S.,, Z. Toossi,, J. L. Johnson,, H. Luzze,, L. Ntambi,, P. Peters,, M. McHugh,, A. Okwera,, M. Joloba,, P. Mugyenyi,, R. D. Mugerwa,, P. Terebuh,, and J. J. Ellner. 2001. Augmentation of apoptosis and interferon-gamma production at sites of active Mycobacterium tuberculosis infection in human tuberculosis. J. Infect. Dis. 183:779788.
64. Hodsdon, W. S.,, H. Luzze,, T. J. Hurst,, M. A. Quigley,, J. Kyosiimire,, P. B. Namujju,, J. L. Johnson,, P. Kaleebu,, A. Okwera,, and A. M. Elliott. 2001. HIV-1-related pleural tuberculosis: elevated production of IFN-gamma, but failure of immunity to Mycobacterium tuberculosis. AIDS 15:467475.
65. Hoheisel, G. B.,, L. Tabak,, H. Teschler,, F. Erkan,, C. Kroegel,, and U. Costabel. 1994. Bronchoalveolar lavage cytology and immunocytology in pulmonary tuberculosis. Am. J. Respir. Crit. Care Med. 149:460463.
66. Holland, S. M.,, E. M. Eisenstein,, D. B. Kuhns,, M. L. Turner,, T. A. Fleisher,, W. Strober,, and J. I. Gallin. 1994. Treatment of refractory disseminated nontuberculous mycobacterial infection with interferon gamma. N. Engl. J. Med. 330:13481355.
67. Holt, P. G. 2000. Antigen presentation in the lung. Am. Respir. Crit. Care Med. 162:S151S156.
68. Houk, V. N.,, J. H. Baker,, K. Sorensen,, and D. C. Kent. 1968. The epidemiology of tuberculosis infection in a closed environment. Arch. Environ. Health 16:2635.
69. Houk, V. N. 1980. Spread of tuberculosis via recirculated air in a naval vessel: the Byrd study. Ann. N.Y. Acad. Sci. 353:1024.
70. 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. Interferonγreceptor deficiency in an infant with fatal Bacille Calmette-Guérin infection. N. Engl. J. Med. 335:19561961.
71. Kaplan, G.,, and V. H. Freedman. 1996. The role of cytokines in the immune response to tuberculosis. Res. Immunol. 147:565572.
72. Keane, J.,, M. K. Malcewicz-Sablinska,, H. G. Remold,, G. L. Chupp,, B. B. Meek,, M. J. Fenton,, and H. Kornfeld. 1997. Infection by Mycobacterium tuberculosis promotes human alveolar macrophage apoptosis. Infect. Immun. 65:289304.
73. Keane, J.,, S. Gershon,, R. P. Wise,, E. Mirabile-Levens,, J. Kasznica,, W. D. Schwieterman,, J. N. Siegel,, and M. M. Braun. 2001. Tuberculosis associated with infliximab, a tumor necrosis factor (alpha)-neutralizing agent. N. Engl. J. Med. 345:10981104.
74. Kindler, V.,, A.-P. Sappino,, G. E. Grau,, P.-F. Piguet,, and P. Vassalli. 1989. The inducing role of tumor necrosis factor in the development of bactericidal granulomas during BCG infection. Cell 56:731740.
75. Kisich, K. O.,, L. Heifets,, M. Higgins,, and G. Diamond. 2001. Antimycobacterial agent based on mRNA encoding human beta-defensin 2 enables primary macrophages to restrict growth of Mycobacterium tuberculosis. Infect. Immun. 69:26922699.
76. Kurashima, K.,, N. Mukaida,, M. Fujimura,, M. Yasui,, Y. Nakazumi,, T. Matsuda,, and K. Matsushima. 1997. Elevated chemokine levels in bronchoalveolar lavage fluid of tuberculosis patients. Am. J. Respir. Crit. Care Med. 155:14741477.
77. Law, K.,, J. Jagirdir,, M. D. Weiden,, M. Bodkin,, and W. N. Rom. 1996. Tuberculosis in HIV-positive patients: cellular response and immune activation in the lung. Am. J. Respir. Crit. Care Med. 153:13771384.
78. Law, K.,, M. Weiden,, T. Harkin,, K. Tchou-Wong,, C. Chi,, and W. N. Rom. 1996. Increased release of interleukin-1β, interleukin-6, and tumor necrosis factor-α by bronchoalveolar cells lavaged from involved sites in pulmonary tuberculosis. Am. J. Respir. Crit. Care Med. 153:799804.
79. Lawn, S. D.,, S. T. Butera,, and T. M. Shinnick. 2002. Tuberculosis unleashed: the impact of human immunodeficiency virus infection on the host granulomatous response to Mycobacterium tuberculosis. Microb. Infect. 4:635646.
80. Light, R. W., 1995. Tuberculous pleural effusions, p. 154166. In D. C. Retford (ed.), Pleural Diseases, 3rd ed. Williams & Wilkins, Baltimore, Md.
81. Lin, Y.,, M. Zhang,, and P. F. Barnes. 1998. Chemokine production by a human alveolar epithelial cell line in response to Mycobacterium tuberculosis. Infect. Immun. 66:11211126.
82. Lorgat, F.,, M. M. Keraan,, and S. R. Ress. 1992. Compartmentalization of the cellular immune response to the recombinant 65 kDa protein of Mycobacterium bovis BCG in patients with tuberculous pleuritis. Reg. Immunol. 4:1217.
83. Loudon, R. G.,, and R. M. Roberts. 1967. Droplet expulsion from the respiratory tract. Am. Rev. Respir. Dis. 95:435442.
84. Lucas, S. B.,, A. Hounnou,, C. Peacock,, A. Beaumel,, G. Djomand,, J. M. N'Gbichi,, K. Yeboue,, M. Honde,, M. Diomande,, C. Giordano,, R. Doorly,, K. Brattegaard,, L. Kestens,, R. Smithwick,, A. Kadio,, N. Ezani,, A. Yapi,, and K. M. De Cock. 1993. The mortality and pathology of HIV infection in a West African city. AIDS 7:15691579.
85. Lucas, S. B.,, and A. M. Nelson,. 1994. Pathogenesis of tuberculosis in human immunodeficiency virus-infected people, p. 503513. In B. R. Bloom (ed.), Tuberculosis: Pathogenesis, Protection, and Control. ASM Press, Washington, D.C.
86. Lucivero, G.,, G. Pierucci,, and L. Bonomo. 1988. Lymphocyte subsets in peripheral blood and pleural fluid. Eur. Resp. J. 1:337340.
87. Maeda, J.,, N. Ueki,, T. Ohkawa,, N. Iwahashi,, T. Nakano,, T. Hada,, and K. Higashino. 1993. Local production and localization of transforming growth factor-beta in tuberculous pleurisy. Clin. Exp. Immunol. 92:3238.
88. Manca, C.,, L. Tsenova,, A. Bergtold,, S. Freeman,, M. Tovey,, J. M. Musser,, C. E. Barry III,, V. H. Freedman,, and G. Kaplan. 2001. 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. Proc. Natl. Acad. Sci. USA 98:57525757.
89. Mehta, P. K.,, C. H. King,, E. H. White,, J. J. Murtagh, Jr.,, and F. D. Quinn. 1996. Comparison of in vitro models for the study of Mycobacterium tuberculosis invasion and intracellular replication. Infect. Immun. 64:26732679.
90. Nau, G. J.,, J. F. L. Richmond,, A. Schlesinger,, E. G. Jennings,, E. S. Lander,, and R. A. Young. 2002. Human macrophage activation programs induced by bacterial pathogens. Proc. Natl. Acad. Sci. USA 99:15031508.
91. Nau, G. J.,, P. Guilfoile,, G. L. Chupp,, J. S. Berman,, J. S. Kim,, H. Kornfeld,, and R. A. Young. 1997. A chemoattractant cytokine associated with granulomas in tuberculosis and silicosis. Proc. Natl. Acad. Sci. USA 94:64146419.
92. Newport, M. J.,, C. M. Huxley,, S. Huston,, C. M. Hawrylowicz,, B. A. Oostra,, R. Williamson,, and M. A. Levin. 1996. A mutation in the interferon-γ-receptor gene and susceptibility to mycobacterial infection. N. Engl. J. Med. 335:19411949.
93. Ni, K.,, and H. C. O'Neill. 1997. The role of dendritic cells in T cell activation. Immunol. Cell. Biol. 75:223230.
94. Nicholson, S.,, M. G. Bonecini-Almeida,, J. R. Lapa e Silva,, C. Nathan,, Q-W. Xie,, R. Mumford,, J. R. Weidner,, J. Calaycay,, J. Geng,, N. Boechat,, C. Linhares,, W. Rom,, and J. L. Ho. 1996. Inducible nitric oxide synthase in pulmonary macrophages from patients with tuberculosis. J. Exp. Med. 183:22932302.
95. Nowakowski, M.,, S. P. Chan,, P. Steiner,, S. Chice,, and H. G. Durkin. 1992. Different distributions of lung and blood lymphocyte subsets in pediatric AIDS or tuberculosis. Ann. Clin. Lab. Sci. 22:377384.
96. Nozaki, Y.,, Y. Hasegawa,, S. Ichiyama,, I. Nakashima,, and K. Shimokata. 1997. Mechanism of nitricoxide-dependent killing of Mycobacterium bovis BCG in human alveolar macrophages. Infect. Immun. 65:36443647.
97. O'Brien, L.,, and P. W. Andrew. 1996. In vitro interaction of Mycobacterium tuberculosis and macrophages: activation of anti-mycobacterial activity of macrophages and mechanisms of anti-mycobacterial activity. Curr. Top. Microbiol. Immunol. 215:97130.
98. Oddo, M.,, T. Renno,, A. Attinger,, T. Bakker,, H. R. MacDonald,, and P. R. A. Meylan. 1998. Fas ligand-induced apoptosis of infected human macrophages reduces the viability of intracellular Mycobacterium tuberculosis. J. Immunol. 160:54485454.
99. Ogawa, K.,, H. Koga,, Y. Hirakata,, K. Tomono,, T. Tashiro,, and S. Kohno. 1997. Differential diagnosis of tuberculous pleurisy by measurement of cytokine concentrations in pleural effusion. Tuber. Lung Dis. 78:2934.
100. Ozaki, T.,, S. Nakahira,, K. Tani,, F. Ogushi,, S. Yasuoka,, and T. Ogura. 1992. Differential cell analysis in bronchoalveolar lavage fluid from pulmonary lesions of patients with tuberculosis. Chest 102:5459.
101. Pettersson, T.,, M. Klockars,, P. E. Hellstroem,, H. Riska,, and A. Wangel. 1978. T and B lymphocytes in pleural effusions. Chest 73:4951.
102. Pitchenik, A. E.,, and H. A. Rubinson. 1985. The radiographic appearance of tuberculosis in patients with the acquired immune deficiency syndrome (AIDS) and pre-AIDS. Am. Rev. Respir. Dis. 131:393396.
103. Ratcliffe, H. L. 1952. Tuberculosis induced by droplet nuclei infection. Am. J. Hyg. 55: 3648.
104. Remoli, M. E.,, E. Giacomini,, G. Lutfalla,, E. Dondi,, G. Orefici,, A. Battistini,, G. Uze,, S. Pellegrini,, and E. M. Coccia. 2002. Selective expression of type I IFN genes in human dendritic cells infected with Mycobacterium tuberculosis. J. Immunol. 169:366374.
105. Ribeiro-Rodrigues R.,, T. Resende Co,, J. L. Johnson,, F. Ribeiro,, M. Palaci,, R. T. Sa,, E. L. Maciel,, F. E. Pereira Lima,, V. Dettoni,, Z. Toossi,, W. H. Boom,, R. Dietze,, J. J. Ellner,, and C. S. Hirsch. 2002. Sputum cytokine levels in patients with pulmonary tuberculosis as early markers of mycobacterial clearance. Clin. Diagn. Lab. Immunol. 9: 818823.
106. Rich, E. A.,, J. R. Panuska,, R. S. Wallis,, C. B. Wolf,, M. L. Leonard,, and J. J. Ellner. 1989. Dyscoordinate expression of tumor necrosis factor-alpha by human blood monocytes and alveolar macrophages. Am. Rev. Respir. Dis. 139:10101016.
107. Rieder, H. L.,, G. M. Cauthen,, G. W. Comstock,, and D. E. Snider, Jr. 1989. Epidemiology of tuberculosis in the United States. Epidemiol. Rev. 11:7998.
108. Riley, R. L.,, and C. C. Mills. 1962. Infectiousness of air from a tuberculosis ward. Am. Rev. Respir. Dis. 85:511525.
109. Robinson, D. S.,, S. Ying,, I. K. Taylor,, A. Wangoo,, D. M. Mitchell,, A. B. Kay,, Q. Hamid,, and R. J. Shaw. 1994. Evidence for a Th1-like bronchoalveolar T-cell subset and predominance of interferon-gamma gene activation in pulmonary tuberculosis. Am. J. Respir. Crit. Care Med. 149:989993.
110. Rouillon, A.,, S. Pedrizet,, and R. Parrot. 1976. Transmission of tubercle bacilli: the effects of chemotherapy. Tubercle 57:275299.
111. Sadek, M.,, E. Sada,, Z. Toossi,, S. K. Schwander,, and E. A. Rich. 1998. Chemokines induced by infection of mononuclear phagocytes with mycobacteria and present in lung alveoli during active pulmonary tuberculosis. Am. J. Respir. Cell Mol. Biol. 19: 513521.
112. Samten, B.,, P. Ghosh,, A-K. Yi,, S. E. Weis,, D. L. Lakey,, R. Gonsky,, U. Pendurthi,, B. Wizel,, Y. Zhang,, M. Zhang,, J. Gong,, M. Fernandez,, H. Safi,, R. Vankayalapati,, H. A. Young,, and P. F. Barnes. 2002. Reduced expression of nuclear cyclic adenosine 5'- monophosphate response element-binding proteins and IFN-γ promoter function in disease due to an intracellular pathogen. J. Immunol. 168:35203526.
113. Schlesinger, L. S. 1993. Macrophage phagocytosis of virulent but not attenuated strains of Mycobacterium tuberculosis is mediated by mannose receptors in addition to complement receptors. J. Immunol. 150:29202930.
114. Schlesinger, L. S.,, C. G. Bellinger-Kawahara,, N. R. Payne,, and M. A. Horwitz. 1990. Phagocytosis of Mycobacterium tuberculosis is mediated by human monocyte complement receptors and complement component 3. J. Immunol. 144:27712780.
115. Schwander, S. K.,, E. Sada,, M. Torres,, D. Escobedo,, J. G. Sierra,, and E. A. Rich. 1996. T Lymphocytic and immature macrophage alveolitis in active pulmonary tuberculosis. J. Infect. Dis. 173:12671272.
116. Schwander, S. K.,, M. Torres,, C. Carranza,, D. Escobedo,, M. Tary-Lehmann,, P. Andersen,, Z. Toossi,, J. J. Ellner,, E. A. Rich,, and E. Sada. 2000. Pulmonary mononuclear cell responses to antigens of Mycobacterium tuberculosis in healthy household contacts of patients with active tuberculosis and healthy controls from the community. J. Immunol. 165:14791485.
117. Schwander, S. K.,, M. Torres,, E. Sada,, C. Carranza,, E. Ramos,, M. Tary-Lehmann,, R. S. Wallis,, J. Sierra,, and E. A. Rich. 1998. Enhanced responses to Mycobacterium tuberculosis antigens by human alveolar lymphocytes during active pulmonary tuberculosis. J. Infect. Dis. 178:14341445.
118. Selwyn, P. A.,, D. Hartel,, V. A. Lewis,, E. E. Schoenbaum,, S. H. Vermund,, R. S. Klein,, A. T. Walker,, and G. H. Friedland. 1989. A prospective study of the risk of tuberculosis among intravenous drug users with human immunodeficiency virus infection. N. Engl. J. Med. 320:545550.
119. Sertl, K.,, T. Takemura,, E. Tschachler,, V. J. Ferrans,, M. A. Kaliner,, and E. M. Shevach. 1986. Dendritic cells with antigen-presenting capability reside in airway epithelium, lung parenchyma, and visceral pleura. J. Exp. Med. 163:436451.
120. Shaw, J. B.,, and N. Wynn-Williams. 1954. Infectivity of pulmonary tuberculosis in relation to sputum status. Am. Rev. Tuberc. 69:723732.
121. Shimokata, K.,, H. Kawachi,, H. Kishimoto,, F. Maeda,, and Y. Ito. 1982. Local cellular immunity in tuberculous pleurisy. Am. Rev. Respir. Dis. 126:822824.
122. Shimokata, K.,, H. Saka,, T. Murate,, Y. Hasegawa,, and T. Hasegawa. 1991. Cytokine content in pleural effusion. Comparison between tuberculous and carcinomatous pleurisy. Chest 99:11031107.
123. Shiratsuchi, H.,, and I. Tsuyuguchi. 1984. Analysis of T cell subsets by monoclonal antibodies in patients with tuberculosis after in vitro stimulation with purified protein derivative of tuberculin. Clin. Exp. Immunol. 57:271278.
124. 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. CD-1 restricted T cell recognition of microbial lipoglycan antigens. Science 269:227230.
125. Small, P. M.,, G. F. Schecter,, P. C. Goodman,, M. A. Sande,, R. E. Chaisson,, and P. C. Hopewell. 1997. Treatment of tuberculosis in patients with advanced human immunodeficiency virus infection. N. Engl. J. Med. 324:289294.
126. Smith, S.,, D. Liggitt,, E. Jeromsky,, X. Tan,, S. J. Skerrett,, and C. B. Wilson. 2002. Local role for tumor necrosis factor alpha in the pulmonary inflammatory response to Mycobacterium tuberculosis infection. Infect. Immun. 70:20822089.
127. Taha, R. A.,, T. C. Kotsimbos,, Y. L. Song,, D. Menzies,, and Q. Hamid. 1997. IFNgamma and IL-12 are increased in active compared with inactive tuberculosis. Am. J. Respir. Crit. Care Med. 155:11351139.
128. Tan, J. S.,, D. H. Canaday,, W. H. Boom,, K. N. Balaji,, S. K. Schwander,, and E. A. Rich. 1997. Human alveolar T lymphocyte responses to Mycobacterium tuberculosis antigens: role for CD4+ and CD8+ cytotoxic T cells and relative resistance of alveolar macrophages to lysis. J. Immunol. 159:290297.
129. Ting, L. M.,, A. C. Kim,, A. Cattamanchi,, and J. D. Ernst. 1999. Mycobacterium tuberculosis inhibits IFN-gamma transcriptional responses without inhibiting activation of STAT-1. J. Immunol. 163:38983906.
130. Toossi, Z.,, B. D. Hamilton,, M. H. Phillips,, L. E. Averill,, J. J. Ellner,, and A. Salvekar. 1997. Regulation of nuclear factor-kappa B and its inhibitor I kappa B-alpha/MAD-3 in monocytes by Mycobacterium tuberculosis and during human tuberculosis. J. Immunol. 159:41094116.
131. Toossi, Z.,, M. E. Kleinhenz,, and J. J. Ellner. 1986. Defective interleukin-2 production and responsiveness in human pulmonary tuberculosis. J. Exp. Med. 163:11621172.
132. Toossi, Z.,, T.-G. Young,, L. E. Averill,, B. D. Hamilton,, H. Shiratsuchi,, and J. J. Ellner. 1995. Induction of transforming growth factor-beta 1 by purified protein derivative (PPD) of Mycobacterium tuberculosis. Infect. Immun. 63:224228.
133. Valdes, L.,, D. Alvarez,, E. San Jose,, P. Penela,, J. M. Valle,, J. M. Garcia-Pazos,, J. Suarez,, and A. Pose. 1998. Tuberculous pleurisy. A study of 254 patients. Arch. Intern. Med. 158:20172021.
134. Vanham, G.,, K. Edmonds,, L. Qing,, D. Hom,, Z. Toossi,, B. Jones,, C. L. Daley,, R. Huebner,, L. Kestens,, P. Gigase,, and J. J. Ellner. 1996. Generalized immune activation in pulmonary tuberculosis: co-activation with HIV infection. Clin. Exp. Immunol. 103: 3034.
135. Wallis, R. S.,, M. Amir-Tahmasseb,, and J. J. Ellner. 1990. Induction of interleukin-1 and tumor necrosis factor by mycobacterial proteins: the monocyte Western blot. Proc. Natl. Acad. Sci. USA 87:33483352.
136. Wang, C. H.,, C. Y. Liu,, H. C. Lin,, C. T. Yu,, K. F. Chung,, and H. P. Kuo. 1998. Increased exhaled nitric oxide in active pulmonary tuberculosis due to inducible NO synthase upregulation in alveolar macrophages. Eur. Respir. J. 11:809815.
137. Wells, W. F.,, H. L. Ratcliffe,, and C. Crumb. 1948. On the mechanics of droplet nuclei infection. II. Quantitative experimental air-borne tuberculosis in rabbits. Am. J. Hyg. 47:1128.
138.World Health Organization/International Union against Tuberculosis and Lung Disease. Anti-Tuberculosis Drug Resistance in the World. Report No. 2. The WHO/IUATLD Global Project on Anti-Tuberculosis Drug Resistance Surveillance 1997-2000. WHO/CDS/ TB/2000.278. World Health Organization, Geneva, Switzerland.
139. Yokoyama, A.,, M. Maryuyama,, M. Ito,, N. Kohno,, K. Hiwada,, and S. Yano. 1992. Interleukin 6 activity in pleural effusion. Its diagnosticvalue and thrombopoieticac tivity. Chest 102:10551059.
140. Zhang, M.,, M. K. Gately,, E. Wang,, J. Gong,, S. F. Wolf,, S. Lu,, R. L. Modlin,, and P. F. Barnes. 1994. Interleukin 12 at the site of disease in tuberculosis. J. Clin. Investig. 93:17331739.
141. Zhang, M.,, Y. Lin,, D. V. Iyer,, J. Gong,, J. S. Abrams,, and P. F. Barnes. 1995. T-cell cytokine responses in human infection with Mycobacterium tuberculosis. Infect. Immun. 63:32313234.
142. Zhang, Y.,, M. Broser,, H. Cophen,, M. Bodkin,, K. Law,, J. Reibman,, and W. M. Rom. 1995


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Table 1

Characterization of alveolar lymphocytes in human pulmonary tuberculosis

Citation: Schwander S, Ellner J. 2003. Human Tuberculosis, p 173-206. In Boros D (ed), Granulomatous Infections and Inflammations. ASM Press, Washington, DC. doi: 10.1128/9781555817879.ch7

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