Chapter 31 : Th1 and Th2 Cytokines in the Human Immune Response to Tuberculosis

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Immune defenses against are mediated primarily by T cells, and IFN-γ is essential for protective immunity. Investigators have studied cytokine production and mRNA expression in bronchoalveolar lavage fluid and in lung tissue from patients with pulmonary tuberculosis, pleural fluid from those with tuberculous pleuritis, and lymph nodes from patients with tuberculous lymphadenitis. Most investigators have reported that peripheral blood mononuclear cells (PBMC) of tuberculosis patients show decreased induced IFN-γ production. Helminthic infections and tuberculosis are both common in developing nations, and current or prior helminthic infections can strongly bias mycobacterial antigen-elicited cytokine production toward a Th2 response. Dysregulation of the systemic Th1 and Th2 cytokine responses may be a secondary effect of tuberculosis, since tuberculosis commonly results in malnutrition, which in turn is associated with enhanced Th2 and reduced Th1 cytokine responses. Local administration of cytokines is theoretically more appealing than systemic therapy, since the former approach is likely to result in fewer side effects.

Citation: Barnes P, Vankayalapati R. 2005. Th1 and Th2 Cytokines in the Human Immune Response to Tuberculosis, p 489-496. In Cole S, Eisenach K, McMurray D, Jacobs, Jr. W (ed), Tuberculosis and the Tubercle Bacillus. ASM Press, Washington, DC. doi: 10.1128/9781555817657.ch31

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Transforming Growth Factor beta
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Cytokine production in human tuberculosis. At the tissue sites of disease, macrophages produce cytokines that favor the production of Th1 cells. Cytokines such as IL-10, IL-18, and IFN-γ leak into the systemic circulation, resulting in high levels in serum. In the blood, monocytes produce TGF-β and IL-10, which favor the development of Th2 cells, resulting in systemic production of IL-4. Elevated cortisol levels and helminthic infections probably contribute to these effects. M?, macrophage.

Citation: Barnes P, Vankayalapati R. 2005. Th1 and Th2 Cytokines in the Human Immune Response to Tuberculosis, p 489-496. In Cole S, Eisenach K, McMurray D, Jacobs, Jr. W (ed), Tuberculosis and the Tubercle Bacillus. ASM Press, Washington, DC. doi: 10.1128/9781555817657.ch31
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1. 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. Kumurante,, and J.-L. Casanova. 1998. Impairment of mycobacterial immunity in human interleukin- 12 receptor deficiency. Science 280:14321435.
2. 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. Tubercle Lung Dis. 80:249258.
3. Baker, R. W.,, B. R. Walker,, R. J. Shaw,, J. W. Honour,, D. S. Jessop,, S. L. Lightman,, A. Zumla,, and G. A. W. Rook. 2000. Increased cortisol:cortisone ratio in acute pulmonary tuberculosis. Am. J. Respir. Crit. Care Med. 162:16411647.
4. 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.
5. Bhattacharyya, S.,, R. Singla,, A. B. Dey,, and H. K. Prasad. 1999. Dichotomy of cytokine profiles in patients and high-risk healthy subjects exposed to tuberculosis. Infect. Immun. 67:55975603.
6. Boussiotis, V.A.,, E. Y. 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. Investig. 105:13171325.
7. Condos, R.,, W. N. Rom,, and N. W. Schluger. 1997. Treatment of multidrug-resistant pulmonary tuberculosis with interferon- gamma via aerosol. Lancet 349:15131515.
8. 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.
9. Dooley, D. P.,, J. L. Carpenter,, and S. Rademacher. 1997. Adjunctive corticosteroid therapy for tuberculosis: a critical reappraisal of the literature. Clin. Infect. Dis. 25:872887.
10. Fenhalls, G.,, L. Stevens,, J. Bezuidenhout,, G. E. Amphlett,, K. Duncan,, P. Bardin,, and P. T. Lukey. 2002. Distribution of IFN-γ, IL-4 and TNF-α protein and CD8 T cells producing IL- 12p40 mRNA in human lung tuberculous granulomas. Immunology 105:325335.
11. Gerosa, F.,, C. Nisii,, S. Righetti,, R. Micciolo,, M. Marchesini,, A. Cazzadori,, and G. Trinchieri. 1999. CD4+ T-cell clones producing both interferon-γ and interleukin-10 predominate in bronchoalveolar lavages of active pulmonary tuberculosis patients. Clin. Immunol. 92:224234.
12. Hirsch, C. S.,, J. J. Ellner,, R. Blinkhorn,, and Z. Toossi. 1997. In vitro restoration of T-cell responses in tuberculosis and augmentation of monocyte effector function against Mycobacterium tuberculosis by natural inhibitors of transforming growth factor β. Proc. Natl. Acad. Sci. USA 94:39263931.
13. 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.
14. 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-γ responses in pulmonary tuberculosis: analysis of underlying mechanisms and modulation with therapy. J. Infect. Dis. 180:20692073.
15. 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.
16. Hoshino, T.,, R. H. Wiltrout,, and H. A. Young. 1999. IL-18 is a potent coinducer of IL-13 in NK and T cells: a new potential role for IL-18 in modulating the immune response. J. Immunol. 162:50705077
17. 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. 78:195203.
18. Lee, B. O.,, L. Haynes,, S. M. Eaton,, S. L. Swain,, and T. D. Randall. 2002. The biological outcome of CD40 signaling is dependent on the duration of CD40 ligand expression: reciprocal regulation by interleukin (IL)-4 and IL-12. J. Exp. Med. 196:693704.
19. Lienhardt, C.,, A. Azzurri,, A. Amedel,, K. Fielding,, J. Sillah,, O. Y. Sow,, B. Bah,, M. Beneglano,, A. Diallo,, R. Manetti,, K. Manneh,, P. Gustafson,, S. Bennett,, M. M. D’Elios,, K. McAdam,, and G. Del Prete. 2002. Active tuberculosis in Africa is associated with reduced Th1 and increased Th2 activity in vivo. Eur. J. Immunol. 32:16051613.
20. Lin, Y.,, M. Zhang,, F. M. Hofman,, J. Gong,, and P. F. Barnes. 1996. Absence of a prominent Th2 cytokine response in human tuberculosis. Infect. Immun. 64:13511356.
21. Lord, G. M.,, G. Matarese,, J. K. Howard,, R. J. Baker,, S. R. Bloom,, and R. I. Lechler. 1998. Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression. Nature 394:897901.
22. Malhotra, I.,, P. Mungai,, A. Wamachi,, J. Kioko,, J. H. Ouma,, J. W. Kazura,, and C. L. King. 1999. Helminth- and bacillus Calmette-Guérin-induced immunity in children sensitized in utero to filariasis and schistosomiasis. J. Immunol. 162:68436848.-
23. Ottenhoff, T. H. M.,, D. Kumararatne,, and J.-L. Casanova. 1998. Novel human immunodeficiencies reveal the essential role of type-I cytokines in immunity to intracellular bacteria. Immunol. Today 19:491494.
24. 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.
25. Rojas, R. E.,, K. N. Balaji,, A. Subramanian,, and W. H. Boom. 1999. Regulation of human CD4+ αβ T-cell-receptor-positive (TCR+) and γδ TCR+ T-cell responses to Mycobacterium tuberculosis by interleukin-10 and transforming growth factor β. Infect. Immun. 67:64616472.
26. Samten, B.,, P. Ghosh,, A. 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′-monophospate response element-binding proteins and IFN-γ promoter function in disease due to an intracellular pathogen. J. Immunol. 168:35203526.
27. Samten, B.,, E. K. Thomas,, J.-H. Gong,, and P. F. Barnes. 2000. Depressed CD40 ligand expression contributes to reduced gamma interferon production in human tuberculosis. Infect. Immun. 68:30023006.
28. Scala, E.,, M. Carbonari,, P. Del Porto,, M. Cibati,, T. Tedesco,, A. M. Mazzone,, R. Paganelli,, and M. Fiorilli. 1998. Lymphocyte activation gene-3 (LAG-3) expression and IFN-γ production are variably coregulated in different human T lymphocyte subpopulations. J. Immunol. 161:489493.
29. Schwander, S. K.,, M. Torres,, C. C. Carranza,, D. Escobedo,, M. Tary-Lehmann,, P. Anderson,, 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.
30. 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.
31. Seah, G. T.,, and G. A. W. Rook. 2001. IL-4 influences apoptosis of mycobacterium-reactive lymphocytes in the presence of TNF-α. J. Immunol. 167:12301237.
32. Seah, G. T.,, G. M. Scott,, and G. A. W. Rook. 2000. Type 2 cytokine gene activation and its relationship to extent of disease in patients with tuberculosis. J. Infect. Dis. 181:385389.
33. Smith, S. M.,, M. R. Klein,, J. Sillah,, K. P. W. J. McAdam,, and H. M. Dockrell. 2002. Decreased IFN-γ and increased IL-4 production by human CD8+ T cells in response to Mycobacterium tuberculosis in tuberculosis patients. Tuberculosis 82:713.
34. Song, C.-H.,, H.-J. Kim,, J.-K. Park,, J.-H. Lim,, U.-O. Kim,, J.-S. Kim,, T.-H. Paik,, K.-Y. Kim,, J.-W. Suhr,, and E.-K. Jo. 2000. Depressed interleukin-12 (IL-12), but not IL-18, production in response to a 30- or 32-kilodalton mycobacterial antigen in patients with active pulmonary tuberculosis. Infect. Immun. 68:44774484.
35. Surcel, H.-M.,, M. Troye-Blomberg,, S. Paulie,, G. Andersson,, C. Moreno,, G. Pasvol,, and J. Ivanyi. 1994. Th1/Th2 profiles in tuberculosis, based on the proliferation and cytokine responses of blood lymphocytes to mycobacterial antigens. Immunology 81:171176.
36. Taha, R. A.,, T. C. Kotsimbos,, Y. Song,, D. Menzies,, and Q. Hamid. 1997. IFN-γ and IL-12 are increased in active compared with inactive tuberculosis. Am. J. Respir. Crit. Care Med. 155:11351139.
37. Ting, L.-M.,, A.C. Kim,, A. Cattamanchi,, and J. D. Ernst. 1999. Mycobacterium tuberculosis inhibits IFN-γ transcriptional responses without inhibiting activation of STAT1. J. Immunol. 163:38983906.
38. Torres, M.,, T. Herrera,, H. Villareal,, E. A. Rich,, and E. Sada. 1998. Cytokine profiles for peripheral blood lymphocytes from patients with active pulmonary tuberculosis and healthy household contacts in response to the 30-kilodalton antigen of Mycobacterium tuberculosis. Infect. Immun. 66:176180.
39. Tsao, T. C. Y.,, C. C. Huang,, W.-K. Chiou,, P.-Y. Yang,, M.-J. Hsieh,, and K.-C. Tsao. 2002. Levels of interferon-γ and interleukin- 2 receptor-α for bronchoalveolar lavage fluid and serum were correlated with clinical grade and treatment of pulmonary tuberculosis. Int. J. Tuberc. Lung Dis. 6:720727.
40. van Creve, R.,, E. Karyadi,, F. Preyers,, M. Leenders,, B.-J. Kullberg,, R. H. H. Nelwan,, and J. W. M. van der Meer. 2000. Increased production of interleukin 4 by CD4+ and CD8+ T cells from patients with tuberculosis is related to the presence of pulmonary cavities. J. Infect Dis. 181:11941197.
41. Vankayalapati, R.,, B. Wizel,, S. E. Weis,, P. Klucar,, H. Shams,, B. Samten,, and P. F. Barnes. 2003. Serum cytokine concentrations do not parallel Mycobacterium tuberculosis-induced cytokine production in patients with tuberculosis. Clin. Infect. Dis. 36:2428.
42. Vankayalapati, R.,, B. Wizel,, S. E. Weis,, B. Samten,, W. M. Girard,, and P. F. Barnes. 2000. Production of interleukin-18 in human tuberculosis. J. Infect. Dis. 182:234239.
43. Verbon, A.,, N. Juffermans,, S. J. H. van Deventer,, P. Speelman,, H. Van Deutekom,, and T. van der Poll. 1999. Serum concentrations of cytokines in patients with active tuberculosis and after treatment. Clin. Exp. Immunol. 115:110113.
44. Wild, J. S.,, A. Sigounas,, N. Sur,, M. S. Siddiqui,, R. Alam,, M. Kurimoto,, and S. Sur. 2000. IFN-γ-inducing factor (IL-18) increases allergic sensitization, serum IgE, Th2 cytokines, and airway eosinophilia in a mouse model of allergic asthma. J. Immunol. 164:27012710.
45. Yamada, G.,, N. Shijubo,, K. Shigehara,, H. Okamura,, M. Kurimoto,, and S. Abe. 2000. Increased levels of circulating interleukin-18 in patients with advanced tuberculosis. Am. J. Respir. Crit. Care Med. 161:17861789.
46. 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.
47. Zhang, M.,, J.-H. Gong,, D. H. Presky,, W. Xue,, and P. F. Barnes. 1999. Expression of the IL-12 receptor β1 and β2 subunits in human tuberculosis. J. Immunol. 162:24412447.
48. 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.
49. Zhang, X.,, T. Brunner,, L. Carter,, R. W. Dutton,, P. Rogers,, L. Bradley,, T. Sato,, J. C. Reed,, D. Green,, and S. L. Swain. 1997. Unequal death in T helper cell (Th)1 and Th2 effectors: Th1, but not Th2, effectors undergo rapid Fas/FasL-mediated apoptosis. J. Exp. Med. 185:18371849.

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