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Published in: European Journal of Clinical Microbiology & Infectious Diseases 6/2010

01-06-2010 | Article

T regulatory cells and Th1/Th2 cytokines in peripheral blood from tuberculosis patients

Authors: X.-Y. He, L. Xiao, H.-B. Chen, J. Hao, J. Li, Y.-J. Wang, K. He, Y. Gao, B.-Y. Shi

Published in: European Journal of Clinical Microbiology & Infectious Diseases | Issue 6/2010

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Abstract

About 10% of people infected with Mycobacterium tuberculosis develop active tuberculosis (TB), and Th1 effector cells and Th1 cytokines play key roles in controlling M. tuberculosis infection. Here, we hypothesise that this susceptibility to M. tuberculosis infection is linked to increased T regulatory (Treg) cells and Th2 cytokines in TB patients. To test this, we recruited 101 participants (71 TB patients, 12 non-TB pulmonary diseases and 18 healthy subjects) and investigated Treg cells and Th1/Th2 cytokines in peripheral blood. CD4+CD25+ T cells and CD4+CD25+FoxP3+ T cells significantly increased and IL-5 dramatically decreased in TB patients relative to healthy subjects. CD8+CD28 T cells, IFN-γ, TNF-α, IL-10 and IL-4 significantly increased in patients with culture and sputum smear-positive pulmonary TB (PTB(+)) compared with healthy subjects. CD4+CD25+FoxP3+ and CD8+CD28 T cells significantly decreased in PTB(+) after one month of chemotherapy. CD4+, CD4+CD25+ and CD8+CD28+ T cells significantly increased in extra-pulmonary TB patients after one month of chemotherapy. These findings suggest that M. tuberculosis infection induces circulating CD4+CD25+FoxP3+ and CD8+CD28 T cell expansion, which may be related to the progression of M. tuberculosis infection, and that the balance between effector immune responses and suppression immune responses is essential to control M. tuberculosis infection.
Literature
1.
go back to reference Ordway D, Henao-Tamayo M, Harton M, Palanisamy G, Troudt J, Shanley C, Basaraba RJ, Orme IM (2007) The hypervirulent Mycobacterium tuberculosis strain HN878 induces a potent TH1 response followed by rapid down-regulation. J Immunol 179:522–531PubMed Ordway D, Henao-Tamayo M, Harton M, Palanisamy G, Troudt J, Shanley C, Basaraba RJ, Orme IM (2007) The hypervirulent Mycobacterium tuberculosis strain HN878 induces a potent TH1 response followed by rapid down-regulation. J Immunol 179:522–531PubMed
2.
go back to reference Chatila TA (2005) Role of regulatory T cells in human diseases. J Allergy Clin Immunol 116:949–959CrossRefPubMed Chatila TA (2005) Role of regulatory T cells in human diseases. J Allergy Clin Immunol 116:949–959CrossRefPubMed
3.
go back to reference Baecher-Allan C, Brown JA, Freeman GJ, Hafler DA (2001) CD4+CD25high regulatory cells in human peripheral blood. J Immunol 167:1245–1253PubMed Baecher-Allan C, Brown JA, Freeman GJ, Hafler DA (2001) CD4+CD25high regulatory cells in human peripheral blood. J Immunol 167:1245–1253PubMed
4.
go back to reference Fontenot JD, Rudensky AY (2005) A well adapted regulatory contrivance: regulatory T cell development and the forkhead family transcription factor Foxp3. Nat Immunol 6:331–337CrossRefPubMed Fontenot JD, Rudensky AY (2005) A well adapted regulatory contrivance: regulatory T cell development and the forkhead family transcription factor Foxp3. Nat Immunol 6:331–337CrossRefPubMed
5.
go back to reference Roncador G, Brown PJ, Maestre L, Hue S, Martínez-Torrecuadrada JL, Ling KL, Pratap S, Toms C, Fox BC, Cerundolo V, Powrie F, Banham AH (2005) Analysis of FOXP3 protein expression in human CD4+CD25+ regulatory T cells at the single-cell level. Eur J Immunol 35:1681–1691CrossRefPubMed Roncador G, Brown PJ, Maestre L, Hue S, Martínez-Torrecuadrada JL, Ling KL, Pratap S, Toms C, Fox BC, Cerundolo V, Powrie F, Banham AH (2005) Analysis of FOXP3 protein expression in human CD4+CD25+ regulatory T cells at the single-cell level. Eur J Immunol 35:1681–1691CrossRefPubMed
6.
go back to reference Roy S, Barnes PF, Garg A, Wu S, Cosman D, Vankayalapati R (2008) NK cells lyse T regulatory cells that expand in response to an intracellular pathogen. J Immunol 180:1729–1736PubMed Roy S, Barnes PF, Garg A, Wu S, Cosman D, Vankayalapati R (2008) NK cells lyse T regulatory cells that expand in response to an intracellular pathogen. J Immunol 180:1729–1736PubMed
7.
go back to reference Chiacchio T, Casetti R, Butera O, Vanini V, Carrara S, Girardi E, Di Mitri D, Battistini L, Martini F, Borsellino G, Goletti D (2009) Characterization of regulatory T cells identified as CD4(+)CD25(high)CD39(+) in patients with active tuberculosis. Clin Exp Immunol 156:463–470CrossRefPubMed Chiacchio T, Casetti R, Butera O, Vanini V, Carrara S, Girardi E, Di Mitri D, Battistini L, Martini F, Borsellino G, Goletti D (2009) Characterization of regulatory T cells identified as CD4(+)CD25(high)CD39(+) in patients with active tuberculosis. Clin Exp Immunol 156:463–470CrossRefPubMed
8.
go back to reference Filaci G, Fenoglio D, Fravega M, Ansaldo G, Borgonovo G, Traverso P, Villaggio B, Ferrera A, Kunkl A, Rizzi M, Ferrera F, Balestra P, Ghio M, Contini P, Setti M, Olive D, Azzarone B, Carmignani G, Ravetti JL, Torre G, Indiveri F (2007) CD8+ CD28− T regulatory lymphocytes inhibiting T cell proliferative and cytotoxic functions infiltrate human cancers. J Immunol 179:4323–4334PubMed Filaci G, Fenoglio D, Fravega M, Ansaldo G, Borgonovo G, Traverso P, Villaggio B, Ferrera A, Kunkl A, Rizzi M, Ferrera F, Balestra P, Ghio M, Contini P, Setti M, Olive D, Azzarone B, Carmignani G, Ravetti JL, Torre G, Indiveri F (2007) CD8+ CD28 T regulatory lymphocytes inhibiting T cell proliferative and cytotoxic functions infiltrate human cancers. J Immunol 179:4323–4334PubMed
9.
go back to reference Chen X, Zhou B, Li M, Deng Q, Wu X, Le X, Wu C, Larmonier N, Zhang W, Zhang H, Wang H, Katsanis E (2007) CD4(+)CD25(+)FoxP3(+) regulatory T cells suppress Mycobacterium tuberculosis immunity in patients with active disease. Clin Immunol 123:50–59CrossRefPubMed Chen X, Zhou B, Li M, Deng Q, Wu X, Le X, Wu C, Larmonier N, Zhang W, Zhang H, Wang H, Katsanis E (2007) CD4(+)CD25(+)FoxP3(+) regulatory T cells suppress Mycobacterium tuberculosis immunity in patients with active disease. Clin Immunol 123:50–59CrossRefPubMed
10.
go back to reference Burl S, Hill PC, Jeffries DJ, Holland MJ, Fox A, Lugos MD, Adegbola RA, Rook GA, Zumla A, McAdam KP, Brookes RH (2007) FOXP3 gene expression in a tuberculosis case contact study. Clin Exp Immunol 149:117–122PubMedCrossRef Burl S, Hill PC, Jeffries DJ, Holland MJ, Fox A, Lugos MD, Adegbola RA, Rook GA, Zumla A, McAdam KP, Brookes RH (2007) FOXP3 gene expression in a tuberculosis case contact study. Clin Exp Immunol 149:117–122PubMedCrossRef
11.
go back to reference Sharma PK, Saha PK, Singh A, Sharma SK, Ghosh B, Mitra DK (2009) FoxP3+ regulatory T cells suppress effector T-cell function at pathologic site in miliary tuberculosis. Am J Respir Crit Care Med 179:1061–1070CrossRefPubMed Sharma PK, Saha PK, Singh A, Sharma SK, Ghosh B, Mitra DK (2009) FoxP3+ regulatory T cells suppress effector T-cell function at pathologic site in miliary tuberculosis. Am J Respir Crit Care Med 179:1061–1070CrossRefPubMed
12.
go back to reference Qin XJ, Shi HZ, Liang QL, Huang LY, Yang HB (2008) CD4+CD25+ regulatory T lymphocytes in tuberculous pleural effusion. Chin Med J (Engl) 121:581–586 Qin XJ, Shi HZ, Liang QL, Huang LY, Yang HB (2008) CD4+CD25+ regulatory T lymphocytes in tuberculous pleural effusion. Chin Med J (Engl) 121:581–586
13.
go back to reference Hougardy JM, Verscheure V, Locht C, Mascart F (2007) In vitro expansion of CD4+CD25highFOXP3+CD127low/− regulatory T cells from peripheral blood lymphocytes of healthy Mycobacterium tuberculosis-infected humans. Microbes Infect 9:1325–1332CrossRefPubMed Hougardy JM, Verscheure V, Locht C, Mascart F (2007) In vitro expansion of CD4+CD25highFOXP3+CD127low/− regulatory T cells from peripheral blood lymphocytes of healthy Mycobacterium tuberculosis-infected humans. Microbes Infect 9:1325–1332CrossRefPubMed
14.
go back to reference Roberts T, Beyers N, Aguirre A, Walzl G (2007) Immunosuppression during active tuberculosis is characterized by decreased interferon-gamma production and CD25 expression with elevated forkhead box P3, transforming growth factor-beta, and interleukin-4 mRNA levels. J Infect Dis 195:870–878CrossRefPubMed Roberts T, Beyers N, Aguirre A, Walzl G (2007) Immunosuppression during active tuberculosis is characterized by decreased interferon-gamma production and CD25 expression with elevated forkhead box P3, transforming growth factor-beta, and interleukin-4 mRNA levels. J Infect Dis 195:870–878CrossRefPubMed
15.
go back to reference Suzuki M, Konya C, Goronzy JJ, Weyand CM (2008) Inhibitory CD8+ T cells in autoimmune disease. Hum Immunol 69:781–789CrossRefPubMed Suzuki M, Konya C, Goronzy JJ, Weyand CM (2008) Inhibitory CD8+ T cells in autoimmune disease. Hum Immunol 69:781–789CrossRefPubMed
16.
go back to reference Tulunay A, Yavuz S, Direskeneli H, Eksioglu-Demiralp E (2008) CD8+CD28−, suppressive T cells in systemic lupus erythematosus. Lupus 17:630–637CrossRefPubMed Tulunay A, Yavuz S, Direskeneli H, Eksioglu-Demiralp E (2008) CD8+CD28, suppressive T cells in systemic lupus erythematosus. Lupus 17:630–637CrossRefPubMed
17.
go back to reference Guyot-Revol V, Innes JA, Hackforth S, Hinks T, Lalvani A (2006) Regulatory T cells are expanded in blood and disease sites in patients with tuberculosis. Am J Respir Crit Care Med 171:803–810CrossRef Guyot-Revol V, Innes JA, Hackforth S, Hinks T, Lalvani A (2006) Regulatory T cells are expanded in blood and disease sites in patients with tuberculosis. Am J Respir Crit Care Med 171:803–810CrossRef
18.
go back to reference Quinn KM, McHugh RS, Rich FJ, Goldsack LM, de Lisle GW, Buddle BM, Delahunt B, Kirman JR (2006) Inactivation of CD4+ CD25+ regulatory T cells during early mycobacterial infection increases cytokine production but does not affect pathogen load. Immunol Cell Biol 84:467–474CrossRefPubMed Quinn KM, McHugh RS, Rich FJ, Goldsack LM, de Lisle GW, Buddle BM, Delahunt B, Kirman JR (2006) Inactivation of CD4+ CD25+ regulatory T cells during early mycobacterial infection increases cytokine production but does not affect pathogen load. Immunol Cell Biol 84:467–474CrossRefPubMed
19.
20.
go back to reference Endsley JJ, Waters WR, Palmer MV, Nonnecke BJ, Thacker TC, Jacobs WR Jr, Larsen MH, Hogg A, Shell E, McAlauy M, Scherer CF, Coffey T, Howard CJ, Villareal-Ramos B, Estes DM (2009) The calf model of immunity for development of a vaccine against tuberculosis. Vet Immunol Immunopathol 128:199–204CrossRefPubMed Endsley JJ, Waters WR, Palmer MV, Nonnecke BJ, Thacker TC, Jacobs WR Jr, Larsen MH, Hogg A, Shell E, McAlauy M, Scherer CF, Coffey T, Howard CJ, Villareal-Ramos B, Estes DM (2009) The calf model of immunity for development of a vaccine against tuberculosis. Vet Immunol Immunopathol 128:199–204CrossRefPubMed
21.
go back to reference Scott-Browne JP, Shafiani S, Tucker-Heard G, Ishida-Tsubota K, Fontenot JD, Rudensky AY, Bevan MJ, Urdahl KB (2007) Expansion and function of Foxp3-expressing T regulatory cells during tuberculosis. J Exp Med 204:2159–2169CrossRefPubMed Scott-Browne JP, Shafiani S, Tucker-Heard G, Ishida-Tsubota K, Fontenot JD, Rudensky AY, Bevan MJ, Urdahl KB (2007) Expansion and function of Foxp3-expressing T regulatory cells during tuberculosis. J Exp Med 204:2159–2169CrossRefPubMed
22.
go back to reference Yu T, Yang YH, Dong DQ (2007) The role of CD8+CD28− regulatory T lymphocytes in pulmonary tuberculosis. Zhonghua Jie He He Hu Xi Za Zhi 30:130–132PubMed Yu T, Yang YH, Dong DQ (2007) The role of CD8+CD28 regulatory T lymphocytes in pulmonary tuberculosis. Zhonghua Jie He He Hu Xi Za Zhi 30:130–132PubMed
23.
go back to reference Jacobsen M, Detjen AK, Mueller H, Gutschmidt A, Leitner S, Wahn U, Magdorf K, Kaufmann SH (2007) Clonal expansion of CD8+ effector T cells in childhood tuberculosis. J Immunol 179:1331–1339PubMed Jacobsen M, Detjen AK, Mueller H, Gutschmidt A, Leitner S, Wahn U, Magdorf K, Kaufmann SH (2007) Clonal expansion of CD8+ effector T cells in childhood tuberculosis. J Immunol 179:1331–1339PubMed
24.
go back to reference Orme IM, Roberts AD, Griffin JP, Abrams JS (1993) Cytokine secretion by CD4 T lymphocytes acquired in response to Mycobacterium tuberculosis infection. J Immunol 151:518–525PubMed Orme IM, Roberts AD, Griffin JP, Abrams JS (1993) Cytokine secretion by CD4 T lymphocytes acquired in response to Mycobacterium tuberculosis infection. J Immunol 151:518–525PubMed
25.
go back to reference Orme IM, Miller ES, Roberts AD, Furney SK, Griffin JP, Dobos KM, Chi D, Rivoire B, Brennan PJ (1992) T lymphocytes mediating protection and cellular cytolysis during the course of Mycobacterium tuberculosis infection. Evidence for different kinetics and recognition of a wide spectrum of protein antigens. J Immunol 148:189–196PubMed Orme IM, Miller ES, Roberts AD, Furney SK, Griffin JP, Dobos KM, Chi D, Rivoire B, Brennan PJ (1992) T lymphocytes mediating protection and cellular cytolysis during the course of Mycobacterium tuberculosis infection. Evidence for different kinetics and recognition of a wide spectrum of protein antigens. J Immunol 148:189–196PubMed
26.
go back to reference Tran DQ, Shevach EM (2009) Therapeutic potential of FOXP3(+) regulatory T cells and their interactions with dendritic cells. Hum Immunol 70:294–299CrossRefPubMed Tran DQ, Shevach EM (2009) Therapeutic potential of FOXP3(+) regulatory T cells and their interactions with dendritic cells. Hum Immunol 70:294–299CrossRefPubMed
Metadata
Title
T regulatory cells and Th1/Th2 cytokines in peripheral blood from tuberculosis patients
Authors
X.-Y. He
L. Xiao
H.-B. Chen
J. Hao
J. Li
Y.-J. Wang
K. He
Y. Gao
B.-Y. Shi
Publication date
01-06-2010
Publisher
Springer-Verlag
Published in
European Journal of Clinical Microbiology & Infectious Diseases / Issue 6/2010
Print ISSN: 0934-9723
Electronic ISSN: 1435-4373
DOI
https://doi.org/10.1007/s10096-010-0908-0

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