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Published in: Respiratory Research 1/2017

Open Access 01-12-2017 | Research

Decreased T helper 17 cells in tuberculosis is associated with increased percentages of programmed death ligand 1, T helper 2 and regulatory T cells

Authors: Chin-Chung Shu, Ming-Fang Wu, Jann-Yuan Wang, Hsin-Chih Lai, Li-Na Lee, Bor-Luen Chiang, Chong-Jen Yu

Published in: Respiratory Research | Issue 1/2017

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Abstract

Background

Tuberculosis (TB) is one of the most common infectious diseases worldwide. During active tuberculosis, T helper (Th) 17 cells are decreased, however the association with inhibitory immune regulation is unclear.

Methods

We enrolled 27 patients with TB and 20 age- and sex-matched controls and studies their lymphocyte status. Peripheral blood lymphocytes were isolated and programmed death-1 (PD-1) and programmed death ligand 1 (PD-L1) were measured on Th17 cells by using flow cytometry after the cells were stimulated with phorbol 12-myristate 13-acetate and ionomycin for 6 h. In addition, Th2 and regulatory T cells were measured and analyzed.

Results

The TB group had lower levels of Th17 cells but higher levels of Th2 and Treg cells than the controls. In Th17 cells, the percentage of PD-L1 was higher in the TB group than that in the controls. In Th2 and Treg cells, the percentage of cytotoxic T-lymphocyte associated protein 4 (CTLA-4) was lower in the TB group and PD-1 was higher in Treg cells in the TB group. In the patients with extra-pulmonary TB, levels of Th1, Th2 and T17 cells were lower than those with pulmonary TB. The percentage of PD-1 on Th1 lymphocytes positively correlated with radiographic score.

Conclusions

Lower level of Th17 in TB patients may be associated with increased percentage of PD-L1 and increasing levels of Th2 and Treg cells which influenced by CTLA-4.
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Literature
1.
go back to reference World Health Organization. Group at risk: WHO report on the tuberculosis epidemic. Geneva, Switzerland: World Health Organization; 1996. World Health Organization. Group at risk: WHO report on the tuberculosis epidemic. Geneva, Switzerland: World Health Organization; 1996.
2.
go back to reference World Health Organization. Global tuberculosis control: surveillance, planning, financing. Geneva, Switzerland: World Health Organization; 2008. World Health Organization. Global tuberculosis control: surveillance, planning, financing. Geneva, Switzerland: World Health Organization; 2008.
3.
go back to reference American Thoracic Society, CDC, and Infectious Diseases Society of America. Treatment of tuberculosis. MMWR Recomm Rep. 2003;52:1–77. American Thoracic Society, CDC, and Infectious Diseases Society of America. Treatment of tuberculosis. MMWR Recomm Rep. 2003;52:1–77.
4.
go back to reference American Thoracic S, Centers for Disease C, Prevention, Infectious Diseases Society of A. American thoracic society/centers for disease control and prevention/infectious diseases society of America: controlling tuberculosis in the united states. Am J Respir Crit Care Med. 2005;172:1169–227.CrossRef American Thoracic S, Centers for Disease C, Prevention, Infectious Diseases Society of A. American thoracic society/centers for disease control and prevention/infectious diseases society of America: controlling tuberculosis in the united states. Am J Respir Crit Care Med. 2005;172:1169–227.CrossRef
5.
go back to reference Luh KT WJ, Wang KF, Chiang CY, Yu MC, Lee JJ, Lee PI, Lee PH, Lin HH, Chiang IH, Hung CC, So R, Chan PC, Su WJ. Taiwan guidelines for TB diangosis and treatment. 5th ed. Taipei: Center for Disease Control, Executive Yuan, Taiwan (R.O.C.); 2015. Luh KT WJ, Wang KF, Chiang CY, Yu MC, Lee JJ, Lee PI, Lee PH, Lin HH, Chiang IH, Hung CC, So R, Chan PC, Su WJ. Taiwan guidelines for TB diangosis and treatment. 5th ed. Taipei: Center for Disease Control, Executive Yuan, Taiwan (R.O.C.); 2015.
7.
go back to reference Cooper AM, Khader SA. The role of cytokines in the initiation, expansion, and control of cellular immunity to tuberculosis. Immunol Rev. 2008;226:191–204.CrossRefPubMedPubMedCentral Cooper AM, Khader SA. The role of cytokines in the initiation, expansion, and control of cellular immunity to tuberculosis. Immunol Rev. 2008;226:191–204.CrossRefPubMedPubMedCentral
8.
go back to reference Korn T, Bettelli E, Oukka M, Kuchroo VK. IL-17 and Th17 Cells. Annu Rev Immunol. 2009;27:485–517.CrossRefPubMed Korn T, Bettelli E, Oukka M, Kuchroo VK. IL-17 and Th17 Cells. Annu Rev Immunol. 2009;27:485–517.CrossRefPubMed
9.
go back to reference Chen X, Zhang M, Liao M, Graner MW, Wu C, Yang Q, Liu H, Zhou B. Reduced Th17 response in patients with tuberculosis correlates with IL-6R expression on CD4+ T Cells. Am J Respir Crit Care Med. 2010;181:734–42.CrossRefPubMed Chen X, Zhang M, Liao M, Graner MW, Wu C, Yang Q, Liu H, Zhou B. Reduced Th17 response in patients with tuberculosis correlates with IL-6R expression on CD4+ T Cells. Am J Respir Crit Care Med. 2010;181:734–42.CrossRefPubMed
10.
go back to reference Xu H, Wang X, Pahar B, Moroney-Rasmussen T, Alvarez X, Lackner AA, Veazey RS. Increased B7-H1 expression on dendritic cells correlates with programmed death 1 expression on T cells in simian immunodeficiency virus-infected macaques and may contribute to T cell dysfunction and disease progression. J Immunol. 2010;185:7340–8.CrossRefPubMedPubMedCentral Xu H, Wang X, Pahar B, Moroney-Rasmussen T, Alvarez X, Lackner AA, Veazey RS. Increased B7-H1 expression on dendritic cells correlates with programmed death 1 expression on T cells in simian immunodeficiency virus-infected macaques and may contribute to T cell dysfunction and disease progression. J Immunol. 2010;185:7340–8.CrossRefPubMedPubMedCentral
11.
go back to reference Okazaki T, Chikuma S, Iwai Y, Fagarasan S, Honjo T. A rheostat for immune responses: the unique properties of PD-1 and their advantages for clinical application. Nat Immunol. 2013;14:1212–8.CrossRefPubMed Okazaki T, Chikuma S, Iwai Y, Fagarasan S, Honjo T. A rheostat for immune responses: the unique properties of PD-1 and their advantages for clinical application. Nat Immunol. 2013;14:1212–8.CrossRefPubMed
12.
go back to reference Singh A, Mohan A, Dey AB, Mitra DK. Inhibiting the programmed death 1 pathway rescues Mycobacterium tuberculosis-specific interferon gamma-producing T cells from apoptosis in patients with pulmonary tuberculosis. J Infect Dis. 2013;208:603–15.CrossRefPubMed Singh A, Mohan A, Dey AB, Mitra DK. Inhibiting the programmed death 1 pathway rescues Mycobacterium tuberculosis-specific interferon gamma-producing T cells from apoptosis in patients with pulmonary tuberculosis. J Infect Dis. 2013;208:603–15.CrossRefPubMed
13.
go back to reference Centers for Disease Control MoHaW, R.O.C. (Taiwan). Taiwan tuberculosis control report 2013. Taiwan: Centers of Disease Control, Department of Health, R.O.C. (Taiwan); 2014. Centers for Disease Control MoHaW, R.O.C. (Taiwan). Taiwan tuberculosis control report 2013. Taiwan: Centers of Disease Control, Department of Health, R.O.C. (Taiwan); 2014.
15.
go back to reference Pitta MG, Romano A, Cabantous S, Henri S, Hammad A, Kouriba B, Argiro L, el Kheir M, Bucheton B, Mary C, et al. IL-17 and IL-22 are associated with protection against human kala azar caused by Leishmania donovani. J Clin Invest. 2009;119:2379–87.PubMedPubMedCentral Pitta MG, Romano A, Cabantous S, Henri S, Hammad A, Kouriba B, Argiro L, el Kheir M, Bucheton B, Mary C, et al. IL-17 and IL-22 are associated with protection against human kala azar caused by Leishmania donovani. J Clin Invest. 2009;119:2379–87.PubMedPubMedCentral
16.
go back to reference Scriba TJ, Kalsdorf B, Abrahams DA, Isaacs F, Hofmeister J, Black G, Hassan HY, Wilkinson RJ, Walzl G, Gelderbloem SJ, et al. Distinct, specific IL-17- and IL-22-producing CD4+ T cell subsets contribute to the human anti-mycobacterial immune response. J Immunol. 2008;180:1962–70.CrossRefPubMedPubMedCentral Scriba TJ, Kalsdorf B, Abrahams DA, Isaacs F, Hofmeister J, Black G, Hassan HY, Wilkinson RJ, Walzl G, Gelderbloem SJ, et al. Distinct, specific IL-17- and IL-22-producing CD4+ T cell subsets contribute to the human anti-mycobacterial immune response. J Immunol. 2008;180:1962–70.CrossRefPubMedPubMedCentral
17.
go back to reference Lyadova IV, Panteleev AV. Th1 and Th17 Cells in Tuberculosis: Protection, Pathology, and Biomarkers. Mediat Inflamm. 2015;2015:854507.CrossRef Lyadova IV, Panteleev AV. Th1 and Th17 Cells in Tuberculosis: Protection, Pathology, and Biomarkers. Mediat Inflamm. 2015;2015:854507.CrossRef
18.
go back to reference Dheda K, Chang JS, Lala S, Huggett JF, Zumla A, Rook GA. Gene expression of IL17 and IL23 in the lungs of patients with active tuberculosis. Thorax. 2008;63:566–8.CrossRefPubMed Dheda K, Chang JS, Lala S, Huggett JF, Zumla A, Rook GA. Gene expression of IL17 and IL23 in the lungs of patients with active tuberculosis. Thorax. 2008;63:566–8.CrossRefPubMed
19.
go back to reference Wang T, Lv M, Qian Q, Nie Y, Yu L, Hou Y. Increased frequencies of T helper type 17 cells in tuberculous pleural effusion. Tuberc (Edinb). 2011;91:231–7.CrossRef Wang T, Lv M, Qian Q, Nie Y, Yu L, Hou Y. Increased frequencies of T helper type 17 cells in tuberculous pleural effusion. Tuberc (Edinb). 2011;91:231–7.CrossRef
20.
go back to reference Kumar NP, Sridhar R, Banurekha VV, Jawahar MS, Nutman TB, Babu S. Expansion of pathogen-specific T-helper 1 and T-helper 17 cells in pulmonary tuberculosis with coincident type 2 diabetes mellitus. J Infect Dis. 2013;208:739–48.CrossRefPubMedPubMedCentral Kumar NP, Sridhar R, Banurekha VV, Jawahar MS, Nutman TB, Babu S. Expansion of pathogen-specific T-helper 1 and T-helper 17 cells in pulmonary tuberculosis with coincident type 2 diabetes mellitus. J Infect Dis. 2013;208:739–48.CrossRefPubMedPubMedCentral
21.
go back to reference Chen YC, Chin CH, Liu SF, Wu CC, Tsen CC, Wang YH, Chao TY, Lie CH, Chen CJ, Wang CC, Lin MC. Prognostic values of serum IP-10 and IL-17 in patients with pulmonary tuberculosis. Dis Markers. 2011;31:101–10.CrossRefPubMedPubMedCentral Chen YC, Chin CH, Liu SF, Wu CC, Tsen CC, Wang YH, Chao TY, Lie CH, Chen CJ, Wang CC, Lin MC. Prognostic values of serum IP-10 and IL-17 in patients with pulmonary tuberculosis. Dis Markers. 2011;31:101–10.CrossRefPubMedPubMedCentral
22.
go back to reference Bandaru A, Devalraju KP, Paidipally P, Dhiman R, Venkatasubramanian S, Barnes PF, Vankayalapati R, Valluri V. Phosphorylated STAT3 and PD-1 regulate IL-17 production and IL-23 receptor expression in Mycobacterium tuberculosis infection. Eur J Immunol. 2014;44:2013–24.CrossRefPubMedPubMedCentral Bandaru A, Devalraju KP, Paidipally P, Dhiman R, Venkatasubramanian S, Barnes PF, Vankayalapati R, Valluri V. Phosphorylated STAT3 and PD-1 regulate IL-17 production and IL-23 receptor expression in Mycobacterium tuberculosis infection. Eur J Immunol. 2014;44:2013–24.CrossRefPubMedPubMedCentral
23.
go back to reference Sharpe AH, Wherry EJ, Ahmed R, Freeman GJ. The function of programmed cell death 1 and its ligands in regulating autoimmunity and infection. Nat Immunol. 2007;8:239–45.CrossRefPubMed Sharpe AH, Wherry EJ, Ahmed R, Freeman GJ. The function of programmed cell death 1 and its ligands in regulating autoimmunity and infection. Nat Immunol. 2007;8:239–45.CrossRefPubMed
24.
go back to reference Dulos J, Carven GJ, van Boxtel SJ, Evers S, Driessen-Engels LJ, Hobo W, Gorecka MA, de Haan AF, Mulders P, Punt CJ, et al. PD-1 blockade augments Th1 and Th17 and suppresses Th2 responses in peripheral blood from patients with prostate and advanced melanoma cancer. J Immunother. 2012;35:169–78.CrossRefPubMed Dulos J, Carven GJ, van Boxtel SJ, Evers S, Driessen-Engels LJ, Hobo W, Gorecka MA, de Haan AF, Mulders P, Punt CJ, et al. PD-1 blockade augments Th1 and Th17 and suppresses Th2 responses in peripheral blood from patients with prostate and advanced melanoma cancer. J Immunother. 2012;35:169–78.CrossRefPubMed
25.
go back to reference Periasamy S, Dhiman R, Barnes PF, Paidipally P, Tvinnereim A, Bandaru A, Valluri VL, Vankayalapati R. Programmed death 1 and cytokine inducible SH2-containing protein dependent expansion of regulatory T cells upon stimulation With Mycobacterium tuberculosis. J Infect Dis. 2011;203:1256–63.CrossRefPubMedPubMedCentral Periasamy S, Dhiman R, Barnes PF, Paidipally P, Tvinnereim A, Bandaru A, Valluri VL, Vankayalapati R. Programmed death 1 and cytokine inducible SH2-containing protein dependent expansion of regulatory T cells upon stimulation With Mycobacterium tuberculosis. J Infect Dis. 2011;203:1256–63.CrossRefPubMedPubMedCentral
26.
go back to reference Alegre ML, Frauwirth KA, Thompson CB. T-cell regulation by CD28 and CTLA-4. Nat Rev Immunol. 2001;1:220–8.CrossRefPubMed Alegre ML, Frauwirth KA, Thompson CB. T-cell regulation by CD28 and CTLA-4. Nat Rev Immunol. 2001;1:220–8.CrossRefPubMed
27.
go back to reference Kumar NP, Sridhar R, Banurekha VV, Nair D, Jawahar MS, Nutman TB, Babu S. Expansion of pathogen-specific mono- and multifunctional Th1 and Th17 cells in multi-focal tuberculous lymphadenitis. PLoS ONE. 2013;8:e57123.CrossRefPubMedPubMedCentral Kumar NP, Sridhar R, Banurekha VV, Nair D, Jawahar MS, Nutman TB, Babu S. Expansion of pathogen-specific mono- and multifunctional Th1 and Th17 cells in multi-focal tuberculous lymphadenitis. PLoS ONE. 2013;8:e57123.CrossRefPubMedPubMedCentral
28.
go back to reference Liao M, Yang Q, Zhang J, Zhang M, Deng Q, Liu H, Graner MW, Kornfeld H, Zhou B, Chen X. Gamma interferon immunospot assay of pleural effusion mononuclear cells for diagnosis of tuberculous pleurisy. Clin Vaccine Immunol. 2014;21:347–53.CrossRefPubMedPubMedCentral Liao M, Yang Q, Zhang J, Zhang M, Deng Q, Liu H, Graner MW, Kornfeld H, Zhou B, Chen X. Gamma interferon immunospot assay of pleural effusion mononuclear cells for diagnosis of tuberculous pleurisy. Clin Vaccine Immunol. 2014;21:347–53.CrossRefPubMedPubMedCentral
29.
go back to reference Kim YK, Lee SY, Kwon SS, Kim KH, Moon HS, Song JS, Park SH. Gamma-interferon and soluble interleukin 2 receptor in tuberculous pleural effusion. Lung. 2001;179:175–84.CrossRefPubMed Kim YK, Lee SY, Kwon SS, Kim KH, Moon HS, Song JS, Park SH. Gamma-interferon and soluble interleukin 2 receptor in tuberculous pleural effusion. Lung. 2001;179:175–84.CrossRefPubMed
Metadata
Title
Decreased T helper 17 cells in tuberculosis is associated with increased percentages of programmed death ligand 1, T helper 2 and regulatory T cells
Authors
Chin-Chung Shu
Ming-Fang Wu
Jann-Yuan Wang
Hsin-Chih Lai
Li-Na Lee
Bor-Luen Chiang
Chong-Jen Yu
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2017
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/s12931-017-0580-3

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