Chapter 25 : T-Cell Responses and Cytokines

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Zoom in

T-Cell Responses and Cytokines, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555818357/9781555819101_Chap25-1.gif /docserver/preview/fulltext/10.1128/9781555818357/9781555819101_Chap25-2.gif


The immune response to tuberculosis is a double-edged sword that may contribute to both clearance of infection and tissue damage. In addition, recent evidence suggests that tuberculosis promotes progression of disease due to human immunodeficiency virus (HIV). Most persons who become infected with mount a protective immune response and remain clinically well, the only evidence of infection being development of a positive tuberculin skin test. Disseminated tuberculosis reflects an ineffective immune response, manifested by a high frequency of negative tuberculin skin tests and failure of T lymphocytes to proliferate in vitro in response to antigens. Tumor necrosis factor (TNF) synergizes with gamma interferon to increase production of nitric oxide metabolites and mycobacterial killing and is essential for granuloma formation to contain mycobacterial infection. Published data on cytokine production by human T cells in response to are conflicting. In patients with tuberculous pleuritis, expression of mRNA for the Th1 cytokines gamma interferon and IL-2 is greater in pleural fluid mononuclear cells than in blood mononuclear cells, and concentrations of gamma interferon are 15-fold higher than those in serum. More comprehensive studies are needed to assess the role of CD8 cells in human antituberculosis defenses. One strategy for developing antituberculosis vaccines is to characterize the T cells and cytokines that mediate clearance of bacilli during the primary immune response as well as the memory T-cell subpopulations and cytokines that protect against tuberculosis from exogenous reinfection and endogenous reactivation.

Citation: Barnes P, Modlin R, Ellner J. 1994. T-Cell Responses and Cytokines, p 417-435. In Bloom B (ed), Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555818357.ch25
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of Figure 1
Figure 1

Cytokine patterns in mycobacterial disease. Reverse transcriptase polymerase chain reaction was used to quantify cytokine mRNA in skin lesions of patients with tuberculoid and lepromatous leprosy. Type 1 cytokines predominate in tuberculoid lepromatous patients, whereas type 2 cytokines are dominant in patients with lepromatous leprosy. IFN-γ, gamma interferon.

Citation: Barnes P, Modlin R, Ellner J. 1994. T-Cell Responses and Cytokines, p 417-435. In Bloom B (ed), Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555818357.ch25
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Abou-Zeid, C.,, T. L. Ratliff,, H. G. Wiker,, M. Harboe,, J. Bennedsen,, and G. A. W. Rook. 1988a. Characterization of fibronectin-binding antigens released by Mycobacterium tuberculosis and Mycobacterium bovis BCG. Infect. Immun. 56: 3046 3051.
2. Abou-Zeid, C.,, I. Smith,, J. M. Grange,, T. L. Ratliff,, J. Steele,, and G. A. W. Rook. 1988b. The secreted antigens of Mycobacterium tuberculosis and their relationship to those recognized by the available antibodies. J. Gen. Microbiol. 134: 531 538.
3. Akbar, A. N.,, M. Salmon,, and G. Janossy. 1991. The synergy between naive and memory T cells during activation. Immunol. Today 12: 184 188.
4. Aldovini, A.,, and R. A. Young. 1991. Humoral and cell-mediated immune responses to live recombinant BCG-HIV vaccines. Nature (London) 351: 479 482.
5. American Thoracic Society. 1986. Treatment of tuberculosis and tuberculosis infection in adults and children. Am. Rev. Respir. Dis. 134: 355363.
6. Augustin, A.,, R. T. Kubo,, and G. K. Sim. 1989. Resident pulmonary lymphocytes expressing the gamma/delta T-cell receptor. Nature (London) 340: 239 241.
7. Aung, H.,, L. E. Averill,, Z. Toossi,, and J. J. Ellner. 1993. Induction of TNF-α from human monocytes stimulated with native 30 kDa antigen of Mycobacterium tuberculosis. Clin. Res. 41: 323A.
8. Barnes, P. F.,, J. S. Abrams,, S. Lu,, P. A. Sieling,, T. H. Rea,, and R. L. Modlin. 1993a. Patterns of cytokine production by mycobacterium-reactive human T cell clones. Infect. Immun. 61: 197 203.
9. Barnes, P. F.,, A. B. Bloch,, P. T. Davidson,, and D. E. Snider, Jr. 1991. Tuberculosis in patients with human immunodeficiency virus infection. N. Engl. J. Med. 324: 1644 1650.
10. Barnes, P. F.,, D. Chatterjee,, J. S. Abrams,, S. Lu,, E. Wang,, M. Yamamura,, P. J. Brennan,, and R. L. Moduli. 1992a. Cytokine production induced by Mycobacterium tuberculosis lipoarabinomannan: relationship to chemical structure. J. Immunol. 307: 1593 1597.
11. Barnes, P. F.,, C. L. Grisso,, J. S. Abrams,, H. Band,, T. H. Rea,, and R. L. Modlin. 1992b. γδ T lymphocytes in human tuberculosis. J. Infect. Dis. 165: 506 512.
12. Barnes, P. F.,, S. Lu,, J. S. Abrams,, E. Wang,, M. Yamamura,, and R. L. Modlin. 1993b. Cytokine production at the site of disease in human tuberculosis. Infect. Immun. 61: 3482 3489.
13. Barnes, P. F.,, V. Mehra,, B. Rivoire,, S.-J. Fong,, P. J. Brennan,, M. S. Voegtline,, P. Minden,, R. A. Hough-ten,, B. R. Bloom,, and R. L. Modlin. 1992c. Immunoreactivity of a 10 kD antigen of Mycobacterium tuberculosis. J. Immunol. 148: 1835 1840.
14. Barnes, P. F.,, S. D. Mistry,, C. L. Cooper,, C. Pirmez,, T. H. Rea,, and R. L. Modlin. 1989a. Compartmentalization of a CD4+ T lymphocyte subpopulation in tuberculous pleuritis. J. Immunol. 142: 1114 1119.
15. Barnes, P. F.,, R. L. Modlin,, D. D. Bikle,, and J. S. Adams. 1989b. Transpleural gradient of 1,25-dihydroxyvitamin D in tuberculous pleuritis. J. Clin. Invest. 83: 1527 1532.
16. Bermudez, L. E. M.,, and L. S. Young. 1988. Tumor necrosis factor, alone or in combination with IL-2, but not IFN--y, is associated with macrophage killing of Mycobacterium avium complex. J. Immunol. 140: 3006 3013.
17. Bermudez, L. E. M.,, and L. S. Young. 1991. Natural killer cell-dependent mycobacteriostatic and mycobactericidal activity in human macrophages. J. Immunol. 146: 265 270.
18. Beutler, B.,, and A. Cerami. 1987. Cachectin: more than a tumor necrosis factor. N. Engl. J. Med. 316: 379 385.
19. Boom, W. H.,, K. A. Chervenak,, M. A. Mincek,, and J. J. Ellner. 1992. Role of the mononuclear phagocyte as an antigen-presenting cell for human γδ T cells activated by live Mycobacterium tuberculosis. Infect. Immun. 60: 3480 3488.
20. Boom, W. H.,, R. S. Wallis,, and K. A. Chervenak. 1991. Human Mycobacterium tuberculosis-reacti\e CD4 + T-cell clones: heterogeneity in antigen recognition, cytokine production, and cytotoxicity for mononuclear phagocytes. Infect. Immun. 59: 2737 2743.
21. Cadranel, J.,, A. J. Hance,, B. Milleron,, F. Paillard,, G. M. Akoun,, and M. Garabedian. 1988. Production of l,25(OH) 2D3 by cells recovered by bronchoalveolar lavage and the role of this metabolite in calcium homeostasis. Am. Rev. Respir. Dis. 138: 984 989.
22. Castro, A. G.,, N. Esaguy,, P. M. Macedo,, A. P. Aguas,, and M. T. Silva. 1991. Live but not heat-killed mycobacteria cause rapid chemotaxis of large numbers of eosinophils in vivo and are ingested by the attracted granulocytes. Infect. Immun. 59: 3009 3014.
23. Centers for Disease Control. 1991. Nosocomial transmission of multidrug-resistant tuberculosis among HIV-infected persons—Florida and New York, 1988-1991. Morbid. Mortal. Weekly Rep. 40: 585591.
24. Chan, J.,, X. Fan,, S. W. Hunter,, P. J. Brennan,, and B. R. Bloom. 1991. Lipoarabinomannan, a possible virulence factor involved in persistence of Mycobacterium tuberculosis within macrophages. Infect. Immun. 59: 1755 1761.
25. Chan, J.,, Y. Xing,, R. S. Magliozzo,, and B. R. Bloom. 1992. Killing of virulent Mycobacterium tuberculosis by reactive nitrogen intermediates produced by activated murine macrophages. J. Exp. Med. 175: 1111 1122.
26. 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.
27. Crowle, A. J.,, and N. Elkins. 1990. Relative permissiveness of macrophages from black and white people for virulent tubercle bacilli. Infect. Immun. 58: 632 638.
28. Dannenberg, A. M. 1991. Delayed-type hypersensitivity and cell-mediated immunity in the pathogenesis of tuberculosis. Immunol. Today 12: 228 233.
29. Davis, M. M.,, and P. J. Bjorkman. 1988. T-cell antigen receptor genes and T-cell recognition. Nature (London) 334: 395 402.
30. de Waal Malefyt, R.,, J. Abrams,, B. Bennett,, C. Figdor,, and J. E. DeVries. 1991. IL-10 inhibits cytokine synthesis by human monocytes: an autocrine role of IL-10 produced by monocytes. J. Exp. Med. 250: 1302 1305.
31. Del Prete, G.,, M. De Carli,, F. Almerigogna,, M. G. Giudizi,, R. Biagotti,, and S. Romagnani. 1993. Human IL-10 is produced by both type 1 helper (Th1) and type 2 helper (Th2) T cell clones and inhibits their antigen-specific proliferation and cytokine production. J. Immunol. 150: 353 360.
32. Del Prete, G. F.,, M. De Carli,, C. Mastromauro,, R. Biagiotti,, D. Macchia,, P. Falagiani,, M. Ricci,, and S. Romagnani. 1991. Purified protein derivative of Mycobacterium tuberculosis and excretory-secretory antigen(s) of Toxocara canis expand in vitro human T cells with stable and opposite (type 1 T helper or type 2 T helper) profile of cytokine production. J. Clin. Invest. 88: 346 350.
33. Dinarello, C. 1984. Interleukin-1 and the pathogenesis of the acute-phase response; N. Engl. J. Med. 311: 1413 1418.
34. Ding, A. H.,, C. Nathan,, J. Graycar,, R. Dernyck,, D. J. Stuehr,, and S. Srimal. 1990. Macrophage deactivating factor and transforming growth factors- B 1 B2, and B 3, inhibit macrophage nitrogen oxide synthesis by interferon--y. J. Immunol. 145: 940 944.
35. Ding, A. H.,, C. F. Nathan,, and D. J. Stuehr. 1988. Release of reactive nitrogen intermediates and reactive oxygen intermediates from mouse peritoneal macrophages: comparison of activating cytokines and evidence for independent production. J. Immunol. 141: 2407 2412.
36. Ellner, J. J. 1978. Suppressor adherent cells in human tuberculosis. J. Immunol. 121: 2573 2578.
37. Fischl, M. A.,, G. L. Daikos,, R. B. Uttamchandani,, R. B. Poblete,, J. N. Moreno,, R. R. Reyes,, A. M. Boota,, L. M. Thompson,, T. J. Cleary,, S. A. Oldham,, M. J. Saldana,, and S. Lai. 1992. Clinical presentation and outcome of patients with HIV infection and tuberculosis caused by multiple-drug-resistant bacilli. Ann. Intern. Med. 117: 184 190.
38. Flesch, I. E.,, and S. H. E. Kaufmann. 1991. Mechanisms involved in mycobacterial growth inhibition by gamma interferon-activated bone marrow macrophages: role of reactive nitrogen intermediates. Infect. Immun. 59: 3213 3218.
39. Flynn, J. L.,, M. M. Goldstein,, K. J. Triebold,, B. Roller,, 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.
40. 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: 73 77.
41. Gajewski, T. F.,, M. Pinnas,, T. Wong,, and F. W. Fitch. 1991. Murine Th1 and Th2 clones proliferate optimally in response to distinct antigen-presenting cell populations. J. Immunol. 146: 1750 1758.
42. Greenbaum, L. A.,, J. B. Horowitz,, A. Woods,, T. Pasqualini,, E.-P. Reich,, and K. Bottomly. 1988. Autocrine growth of CD4 + T cells: differential effects of IL-1 on helper and inflammatory T cells. J. Immunol. 140: 1555 1560.
43. Griffin, J. P.,, K. V. Harshan,, W. K. Born,, and I. M. Orme. 1991. Kinetics of accumulation of gamma/ delta receptor-bearing T lymphocytes in mice infected with live mycobacteria. Infect. Immun. 59: 4263 4265.
44. Haanen, J. B. A. G.,, R. de Waal Malefljt,, P. C. M. Res,, E. M. Kraakman,, T. H. M. Ottenhoff,, R. R. P. de Vries,, and H. Spits. 1991. Selection of a human T helper type 1-like T cell subset by mycobacteria. J. Exp. Med. 174: 583 592.
45. Havlir, D. V.,, J. J. Ellner,, K. Chervenak,, and W. H. Boom. 1991a. Selective expansion of human γδ T cells by monocytes infected with live Mycobacterium tuberculosis. J. Clin. Invest. 87: 729 733.
46. Havlir, D. V.,, F. van der Kuyp,, E. Duffy,, R. Marshall,, D. Horn,, and J. J. Ellner. 1991b. A 19-year follow-up of tuberculin reactors: assessment of skin test reactivity and in vitro lymphocyte responses. Chest 99: 1172 1176.
47. Havlir, D. V.,, R. S. Wallis,, W. H. Boom,, T. M. Daniel,, K. Chervenak,, and J. J. Ellner. 1991c. Human immune response to Mycobacterium tuberculosis antigens. Infect. Immun. 59: 665 670.
48. Heinzel, F. P.,, M. D. Sadick,, B. J. Holaday,, R. L. Coffman,, and R. M. Locksley. 1989. Reciprocal expression of interferon gamma or interleukin 4 during the resolution or progression of murine leishmaniasis: evidence for expansion of distinct helper T cell subsets. J. Exp. Med. 169: 59 72.
49. Heinzel, F. P.,, D. S. Schoenhaut,, M. Rerko,, L. E. Rosser,, and M. K. Gately. 1993. Recombinant interleukin 12 cures mice infected with Leishmania major. J. Exp. Med. 177: 1505 1509.
50. Hirano, T.,, S. Akira,, T. Taga,, and T. Kishimoto. 1990. Biological and clinical aspects of interleukin 6. Immunol. Today 11: 443 449.
51. Ho, L. H.,, S. H. He,, M. J. C. Rios,, and E. A. Wick. 1992. Interleukin-4 inhibits human macrophage activation by tumor necrosis factor, granulocyte- monocyte colony-stimulating factor, and interleukin-3 for antileishmanial activity and oxidative burst capacity. J. Infect. Dis. 165: 344 351.
52. Hsieh, C. S.,, S. E. Macatonia,, C. S. Tripp,, S. F. Wolf,, A. O'Garra,, and K. M. Murphy. 1993. Development of Th1 CD4 + T cells through IL-12 produced by Listeria-induced macrophages. Science 260: 547 549.
53. Huygen, K.,, D. Abramowicz,, P. Vandenbussche,, F. Jacobs,, J. DeBruyn,, A. Kentos,, A. Drowart,, J. P. VanVooren,, and M. Goldman. 1992. Spleen cell cytokine secretion in Mycobacterium bovis BCG-infected mice. Infect. Immun. 60: 2880 2886.
54. Huygen, K.,, J. P. Van Vooren,, M. Turneer,, R. Bos-mans,, P. Dierckx,, and J. De Bruyn. 1988. Specific lymphoproliferation, gamma interferon production, and serum immunoglobulin G directed against a purified 32 kDa mycobacterial protein antigen (P32) in patients with active tuberculosis. Scand. J. Immunol. 27: 187 194.
55. Janis, E. M.,, S. H. Kaufmann,, R. H. Schwartz,, and D. M. Pardoll. 1989. Activation of γδ T cells in the primary immune response to Mycobacterium tuberculosis. Science 244: 713 716.
56. Jones, B. E.,, S. M. M. Young,, D. Antoniskis,, P. T. Davidson,, F. Kramer,, and P. F. Barnes. 1993. Relationship of the manifestations of tuberculosis to CD4 cell counts in patients with human immunodeficiency virus infection. Am. Rev. Respir. Dis. 148: 1292 1297.
57. Kabelitz, D.,, A. Bender,, S. Schondelmaier,, B. Schoel,, and S. H. E. Kaufmann. 1990. A large fraction of human peripheral blood γδ + T cells is activated by Mycobacterium tuberculosis but not by its 65-kD heat shock protein. J. Exp. Med. 171: 667 679.
58. Kaplan, G.,, W. J. Britton,, G. E. Hancock,, W. J. Theuvenet,, K. A. Smith,, C. K. Job,, P. W. Roche,, A. Molloy,, R. Burkhardt,, J. Barker,, H. M. Pradhan,, and Z. A. Conn. 1991. The systemic influence of recombinant interleukin 2 on the manifestations of lepromatous leprosy. J. Exp. Med. 173: 993 1006.
59. Kaufmann, S. H. E. 1988. CD8+ T lymphocytes in intracellular microbial infections. Immunol. Today 9: 168 174.
60. Kaufmann, S. H. E. 1990. Heat shock proteins and the immune response. Immunol. Today 11( 4): 129 136.
61. 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: 731 740.
62. Lederman, M. M.,, D. Georges,, D. Kusher,, C. Z. Giam,, and Z. Toossi. Mycobacterium tuberculosis and its purified protein derivative activate expression of the human immunodeficiency virus. Submitted for publication.
63. Lehn, M.,, W. Y. Weisner,, S. Engelhorn,, S. Gillis,, and H. G. Remold. 1989. IL-4 inhibits H 2O2 production and antileishmanial capacity of human cultured monocytes mediated by IFN-gamma. J. Immunol. 143: 3020 3024.
64. Lorgat, F.,, M. M. Keraan,, P. T. Lukey,, and S. R. Ress. 1992. Evidence for in vivo generation of cytotoxic T cells: PPD-stimulated lymphocytes from tuberculous pleural effusions demonstrate enhanced cytotoxicity with accelerated kinetics of induction. Am. Rev. Respir. Dis. 145: 418 423.
65. Maeda, J.,, N. Ueki,, T. Ohkawa,, N. Iwahashi,, T. Nakano,, T. Hada,, and K. Higashino. 1993. Local production and localization of transforming growth factor-β in tuberculous pleurisy. Clin. Exp. Immunol. 92: 32 38.
66. Maggi, E.,, P. Parronchi,, R. Manetti,, C. Simonelli,, M.-P. Piccinni,, F. S. Rugiu,, M. De Carli,, M. Ricci,, and S. Romagnani. 1992. Reciprocal regulatory effects of IFN-γ and IL-4 on the in vitro development of human Th1 and Th2 clones. J. Immunol. 148: 2142 2147.
67. Manetti, R.,, P. Parronchi,, M. G. Giudizi,, M. P. Piccinni,, E. Maggi,, G. Trinchieri,, and S. Romagnani. 1993. Natural killer cell stimulatory factor (interleukin 12 [IL-12]) induces T helper type 1 (Th1)-specific immune responses and inhibits the development of IL-4-producing Th cells. J. Exp. Med. 177: 1199 1204.
68. Martinez, O. M.,, R. S. Gibbons,, M. R. Garovoy,, and F. R. Aronson. 1990. IL-4 inhibits IL-2 receptor expression and IL-2-dependent proliferation of human T cells. J. Immunol. 144: 2211 2215.
69. Matsuyama, T.,, N. Kobayashi,, and N. Yamamoto. 1991. Cytokines and HIV infection: is AIDS a tumor necrosis factor disease? AIDS 5: 1405 1417.
70. May, M. E.,, and P. J. Spagnuolo. 1987. Evidence for activation of a respiratory burst in the interaction of human neutrophils with Mycobacterium tuberculosis. Infect. Immun. 55: 2304 2307.
71. Modlin, R. L.,, C. Pirmez,, F. M. Hofman,, V. Torigian,, K. Uyemura,, T. H. Rea,, B. R. Bloom,, and M. B. Brenner. 1989. Lymphocytes bearing antigen-specific γδ T-cell receptors accumulate in human infectious disease lesions. Nature (London) 339: 544 548.
72. Moreno, C.,, A. Mehlert,, and J. Lamb. 1988. The inhibitory effects of mycobacterial lipoarabinomannan and polysaccharides upon polyclonal and monoclonal human T cell proliferation. Clin. Exp. Immunol. 74: 206 210.
73. Mosmann, T. R.,, and K. W. Moore. 1991. The role of IL-10 in crossregulation of Th1 and Th2 responses. Immunol. Today 12: A49 A53.
74. Muller, I.,, S. P. Cobbold,, H. Waldmann,, and S. H. E. Kaufmann. 1987. Impaired resistance to Mycobacterium tuberculosis infection after selective in vivo depletion of L3T4 + and Lyt-2 + T cells. Infect. Immun. 55: 2037 2041.
75. Munk, M. E.,, A. J. Gatrill,, and S. H. E. Kaufmann. 1990. Target cell lysis and IL-2 secretion by gamma/ delta T lymphocytes after activation with bacteria. J. Immunol. 145: 2434 2439.
76. Nathan, C. F.,, G. Kaplan,, W. R. Levis,, A. Nusrat,, M. D. Witmer,, S. A. Sherwin,, C. K. Job,, C. R. Horowitz,, R. M. Steinman,, and Z. A. Cohn. 1986. Local and systemic effects of intradermal recombinant interferon-γ in patients with lepromatous leprosy. N. Engl. J. Med. 315: 6 15.
77. O'Brien, R. L.,, M. P. Happ,, A. DaUas,, E. Palmer,, R. Kubo,, and W. K. Born. 1989. Stimulation of a major subset of lymphocytes expressing T cell receptor gamma delta by an antigen derived from Mycobacterium tuberculosis. Cell 57: 667 674.
78. Ogawa, T.,, H. Uclieda,, Y. Kusumoto,, Y. Mori,, Y. Yamamura,, and S. Hamada. 1991. Increase in tumor necrosis factor alpha and interleukin-6 secreting cells in peripheral blood mononuclear cells from subjects infected with Mycobacterium tuberculosis. Infect. Immun. 59: 3021 3025.
79. Ohmen, J. D.,, P. F. Barnes,, C. L. Grisso,, B. R. Bloom,, and R. L. Modlin. Expansion of T cells bearing the Vp8 T cell receptor by Mycobacterium tuberculosis. Submitted for publication.
80. Ohmen, J. D.,, P. F. Barnes,, K. Uyemura,, S. Lu,, C. L. Grisso,, and R. L. Modlin. 1991. The T-cell receptor of human γδ T-cells reactive to Mycobacterium tuberculosis are encoded by specific V genes but diverse V-J junctions. J. Immunol. 50: 361 362.
81. Orme, I. M. 1987. The kinetics of emergence and loss of mediator T lymphocytes acquired in response to infection with Mycobacterium tuberculosis. J. Immunol. 138: 293 298.
82. Orme, I. M. 1988a. Characteristics and specificity of acquired immunologic memory to Mycobacterium tuberculosis infection. J. Immunol. 140: 3589 3593.
83. Orme, I. M. 1988b. Induction of nonspecific acquired resistance and delayed-type hypersensitivity, but not specific acquired resistance, in mice inoculated with killed mycobacterial vaccines. Infect. Immun. 56: 3310 3312.
84. Orme, I. M.,, and F. M. Collins. 1983. Protection against Mycobacterium tuberculosis infection by adoptive immunotherapy. J. Exp. Med. 158: 74 83.
85. Orme, I. M.,, and F. M. Collins. 1984. Adoptive protection of the Mycobacterium tuberculosis-infected lung: dissociation between cells that passively transfer protective immunity and those that transfer delayed-type hypersensitivity. Cell. Immunol. 84: 113 120.
86. Orme, I. M.,, E. S. Miller,, A. D. Roberts,, S. K. Furney,, J. P. Griffin,, K. M. Dobos,, D. Chi,, B. Rivoire,, and P. J. Brennan. 1992. T lymphocytes mediating protection and cellular cytolysis during the course of Mycobacterium tuberculosis infection. J. Immunol. 148: 189 196.
87. Ottenhoff, T. H. M.,, and T. Mutis. 1990. Specific killing of cytotoxic T cells and antigen-presenting cells by CD4 + cytotoxic T cell clones. J. Exp. Med. 171: 2011 2024.
88. Pal, P. G.,, and M. A. Horwitz. 1992. Immunization with extracellular proteins of Mycobacterium tuberculosis induces cell-mediated immune responses and substantial protective immunity in a guinea pig model of pulmonary tuberculosis. Infect. Immun. 60: 4781 4792.
89. Palladino, M. A.,, R. E. Morris,, and A. D. Levinson. 1990. TGFps: a new family of immunoregulatory molecules. Ann. N.Y. Acad. Sci. 593: 181 187.
90. Pedrazzini, T.,, K. Hug,, and J. A. Louis. 1987. Importance of L3T4+ and Lyt-2+ cells in the immunologic control of infection with Mycobacterium bovis strain bacillus Calmette-Guerin in mice. J. Immunol. 139: 2032 2037.
91. Pfeffer, K.,, B. Schoel,, H. Guile,, S. H. E. Kaufmann,, and H. Wagner. 1990. Primary responses of human T cells to mycobacteria: a frequent set of γδ T cells are stimulated by protease-resistant ligands. Eur. J. Immunol. 20: 1175 1179.
92. Platt, J.,, B. W. Grant,, A. A. Eddy,, and A. F. Michael. 1983. Immune cell populations in cutaneous delayed-type hypersensitivity. J. Exp. Med. 158: 1227 1242.
93. Roach, 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, K.C, JE, and tumor necrosis factor-α. J. Immunol. 150: 1886 1896.
94. Rocken, M.,, J.-H. Saurat,, and C. Hauser. 1992. A common precursor for CD4 + T cells producing IL-2 or IL-4. J. Immunol. 148: 1031 1036.
95. Rook, G. A. W.,, J. Steele,, L. Fraher,, S. Barker,, R. Karmali,, and J. O'Riordan. 1986. Vitamin D 3, gamma interferon, and control of proliferation of Mycobacterium tuberculosis by human monocytes. Immunology 57: 159 163.
96. Roper, W. H.,, and J. J. Waring. 1955. Primary serofibrinous pleural effusion in military personnel. Am. Rev. Tuberc. 71: 616 634.
97. Salgame, P.,, J. Abrams,, C. Clayberger,, H. Goldstein,, J. Convit,, R. L. Modlin,, and B. R. Bloom. 1991. Differing lymphokine profiles of functional subsets of human CD4 and CD8 T cell clones. Science 254: 279 281.
98. Sampaio, E. P.,, A. L. Moreira,, E. N. Sarno,, A. M. Malta,, and G. Kaplan. 1992. Prolonged treatment with recombinant interferon gamma induces erythema nodosum leprosum in lepromatous leprosy patients. J. Exp. Med. 175: 1729 1737.
99. Scott, P. 1993. IL-12: initiation cytokine for cell-mediated immunity. Science 260: 496 497.
100. Scott, P.,, P. Natovitz,, R. L. Coffman,, E. Pearce,, and A. Sher. 1988. Immunoregulation of cutaneous leishmaniasis. J. Exp. Med. 168: 1675 1684.
101. Seder, R. A.,, W. E. Paul,, M. M. Davis,, and B. Fazekas de St.Groth. 1992. The presence of interleukin 4 during in vitro priming determines the lymphokine-producing potential of CD4 + T cell receptor transgenic mice. J. Exp. Med. 176: 1091 1098.
102. Stanford, J. L.,, G. M. Bahr,, G. A. W. Rook,, M. A. Shaaban,, T. D. Chugh,, M. Gabriel,, B. Al-Shimali,, Z. Siddiqui,, F. Ghardani,, A. Shahin,, and K. Behbehani. 1990. Immunotherapy with Mycobacterium vaccae as an adjunct to chemotherapy in the treatment of pulmonary tuberculosis. Tubercle 71: 87 93.
103. Stead, W. W.,, J. P. Lofgren,, H. L. Masters,, G. L. Templeton,, M. D. Cave,, and L. A. Illing. An attempt to quantify protection against exogenous reinfection tuberculosis in healthy persons. Submitted for publication.
104. Stead, W. W.,, J. W. Senner,, W. T. Reddick,, and J. P. Lofgren. 1990. Racial differences in susceptibility to infection by Mycobacterium tuberculosis. N. Engl. J. Med. 322: 422 427.
105. Stover, C. K.,, V. F. de la Cruz,, T. R. Fuerst,, J. E. Burlein,, L. A. Benson,, L. T. Bennett,, G. P. Bansai,, J. F. Young,, M. H. Lee,, G. F. Hatfull,, S. B. Snapper,, R. G. Barletta,, W. R. Jacobs, Jr.,, and B. R. Bloom. 1991. New use of BCG for recombinant vaccines. Nature (London) 351: 456 460.
106. Street, N. E.,, and T. R. Mosmann. 1991. Functional diversity of T lymphocytes due to secretion of different cytokine patterns. FASEB J. 5: 171 175.
107. Strominger, J. L. 1989. The gamma delta T cell receptor and class lb MHC-related proteins: enigmatic molecules of immune recognition. Cell 57: 895 898.
108. Takashima, S.,, C. Ueta,, I. Tsuyuguchi,, and S. Kishimuto. 1990. Production of tumor necrosis factor by monocytes from patients with pulmonary tuberculosis. Infect. Immun. 58: 3286 3292.
109. Tazi, A.,, F. Bouchonnet,, D. Valeyre,, J. Cadranel,, J. P. Battesti,, and A. J. Hance. 1992. Characterization of γδ T-lymphocytes in the peripheral blood of patients with active tuberculosis: a comparison with normal subjects and patients with sarcoidosis. Am. Rev. Respir. Dis. 146: 1216 1221.
110. Tazi, A.,, I. Fajac,, P. Soler,, D. Valeyre,, J. P. Battesti,, and A. J. Hance. 1991. Gamma/delta T-lymphocytes are not increased in number in granulomatous lesions of patients with tuberculosis or sarcoidosis. Am. Rev. Respir. Dis. 144: 1373 1375.
111. Toossi, Z.,, M. E. Kleinhenz,, and J. J. Ellner. 1986. Defective interleukin-2 production and responsiveness in human pulmonary tuberculosis. J. Exp. Med. 163: 1162 1172.
112. Toossi, Z.,, J. R. Sedor,, J. P. Lapurge,, R. J. Ondash,, and J. J. Ellner. 1990. Expression of functional interleukin 2 receptors by peripheral blood monocytes from patients with active pulmonary tuberculosis. J. Clin. Invest. 85: 1777 1784.
113. Toossi, Z.,, J. G. Sierra-Madero,, R. A. Blinkhorn,, M. A. Mettler,, and E. A. Rich. 1993. Enhanced susceptibility of blood monocytes from patients with pulmonary tuberculosis to productive infection with human immunodeficiency virus type l.J. Exp. Med. 177: 1511 1516.
114. Toossi, Z.,, T. Young,, P. Gogate,, and J. J. Ellner. 1991. Expression of transforming growth factor-p in lung granulomas and peripheral blood monocytes of patients with tuberculosis, abstr., p. 57 62. Twenty-Sixth Joint Conf. Tuberc. Lepr.
115. Tsicopoulos, A.,, Q. Hamid,, V. Varney,, S. Ying,, R. Moqbel,, S. R. Durham,, and A. B. Kay. 1992. Preferential messenger RNA expression of Th1-type cells (IFN-gamma +, IL-2 +) in classical delayed-type (tuberculin) hypersensitivity reactions in human skin. J. Immunol. 148: 2058 2061.
116. Tsunawaki, S.,, M. Sporn,, A. Ding,, and C. Nathan. 1988. Deactivation of macrophages by transforming growth factor 6. Nature (London) 334: 260 262.
117. Tsuyuguchi, I.,, H. Kawasumi,, C. Ueta,, I. Yano,, and S. Kishimoto. 1991. Increase of T-cell receptor gamma/ delta-bearing T cells in cord blood of newborn babies obtained by in vitro stimulation with mycobacterial cord factor. Infect. Immun. 59: 3053 3059.
118. Tweardy, D. J.,, B. Z. Schacter,, and J. J. Ellner. 1984. Association of altered dynamics of monocyte expression of human leukocyte antigen-DR with immunosuppression in tuberculosis. J. Infect. Dis. 149: 31 37.
119. Valone, S. E.,, E. A. Rich,, R. S. Wallis,, and J. J. Ellner. 1988. Expression of tumor necrosis factor in vitro by human mononuclear phagocytes stimulated with whole Mycobacterium bovis BCG and mycobacterial antigens. Infect. Immun. 56: 3313 3315.
120. Vjecha, M.,, A. Okwera,, F. Byekwaso,, J. Kakibali,, S. Nyole,, M. Okot-Nwang,, T. Avu,, P. Eriki,, R. Mujeuwa,, T. Daniel,, R. Huebner,, and J. J. Ellner. 1992. Predictors of mortality and drug toxicity in HIV-infected patients from Uganda treated for pulmonary tuberculosis, abstr. B180. Abstr. VIII Int. Conf. AIDS/HI STD World Congr..
121. Wallis, R. S.,, R. Paranjape,, and M. Phillips. 1993a. Identification by two-dimensional gel electrophoresis of a 58-kilodalton tumor necrosis factor-inducing protein of Mycobacterium tuberculosis. Infect. Immun. 61: 627 632.
122. Wallis, R. S.,, M. Vjecha,, M. Amir-Tahmasseb,, A. Okwera,, F. Byekwaso,, S. Nyole,, S. Kabengera,, R. D. Mugerwa,, and J. J. Ellner. 1993b. Influence of tuberculosis on human immunodeficiency virus (HIV-1): enhanced cytokine expression and elevated 3 2-microglobulin in HIV-1-associated tuberculosis. J. Infect. Dis. 167: 43 48.
123. Whalen, C.,, C. R. Horsburgh, Jr.,, D. Horn,, C. Labart,, S. Simberkoff,, and J. J. Ellner. 1993. Accelerated clinical course of human immunodeficiency virus infection following active tuberculosis. Clin. Res. 41: 290A.
124. Yamamura, M.,, K. Uyemura,, R. J. Deans,, K. Weinberg,, T. H. Rea,, B. R. Bloom,, and R. L. Modlin. 1991. Defining protective responses to pathogens: cytokine profiles in leprosy lesions. Science 254: 277 279.
125. Yssel, H.,, R. de Waal Malefyt,, M. G. Roncarolo,, J. S. Abrams,, R. Lahesmaa,, H. Spits,, and J. E. de Vries. 1992. IL-10 is produced by subsets of human CD4 T cell clones and peripheral blood T cells. J. Immunol. 149: 2378 2384.
126. Zhang, M.,, M. K. Gately,, E. Wang,, S. F. Wolf,, S. Lu,, R. L. Modlin,, and P. F. Barnes. Interleukin-12 at the site of disease in tuberculosis. J. Clin. Invest., in press.
127. Zumla, A. 1992. Superantigens, T cells, and microbes. Clin. Infect. Dis. 15: 313 320.


Generic image for table
Table 1

Cytokines produced by macrophages and by Th1 and Th2 cells

Citation: Barnes P, Modlin R, Ellner J. 1994. T-Cell Responses and Cytokines, p 417-435. In Bloom B (ed), Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555818357.ch25

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error