Advertisement

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

  • X.-Y. HeEmail author
  • L. Xiao
  • H.-B. Chen
  • J. Hao
  • J. Li
  • Y.-J. Wang
  • K. He
  • Y. Gao
  • B.-Y. Shi
Article

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.

Keywords

Tuberculosis Treg Cell FoxP3 Expression Effector Immune Response Cytometric Bead Array 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

This study was funded by grants from the Ministry of Science and Technology of China (2006AA02Z465) and the People’s Liberation Army (06M302).

Conflict of interest

We assure that, as the authors of this paper, we have a financial relationship with the organisation that sponsored the research. We also declare that we have no conflict of interest.

References

  1. 1.
    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 179:522–531PubMedGoogle Scholar
  2. 2.
    Chatila TA (2005) Role of regulatory T cells in human diseases. J Allergy Clin Immunol 116:949–959CrossRefPubMedGoogle Scholar
  3. 3.
    Baecher-Allan C, Brown JA, Freeman GJ, Hafler DA (2001) CD4+CD25high regulatory cells in human peripheral blood. J Immunol 167:1245–1253PubMedGoogle Scholar
  4. 4.
    Fontenot JD, Rudensky AY (2005) A well adapted regulatory contrivance: regulatory T cell development and the forkhead family transcription factor Foxp3. Nat Immunol 6:331–337CrossRefPubMedGoogle Scholar
  5. 5.
    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 35:1681–1691CrossRefPubMedGoogle Scholar
  6. 6.
    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 180:1729–1736PubMedGoogle Scholar
  7. 7.
    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 156:463–470CrossRefPubMedGoogle Scholar
  8. 8.
    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 179:4323–4334PubMedGoogle Scholar
  9. 9.
    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 123:50–59CrossRefPubMedGoogle Scholar
  10. 10.
    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 149:117–122PubMedCrossRefGoogle Scholar
  11. 11.
    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 179:1061–1070CrossRefPubMedGoogle Scholar
  12. 12.
    Qin XJ, Shi HZ, Liang QL, Huang LY, Yang HB (2008) CD4+CD25+ regulatory T lymphocytes in tuberculous pleural effusion. Chin Med J (Engl) 121:581–586Google Scholar
  13. 13.
    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 9:1325–1332CrossRefPubMedGoogle Scholar
  14. 14.
    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 195:870–878CrossRefPubMedGoogle Scholar
  15. 15.
    Suzuki M, Konya C, Goronzy JJ, Weyand CM (2008) Inhibitory CD8+ T cells in autoimmune disease. Hum Immunol 69:781–789CrossRefPubMedGoogle Scholar
  16. 16.
    Tulunay A, Yavuz S, Direskeneli H, Eksioglu-Demiralp E (2008) CD8+CD28, suppressive T cells in systemic lupus erythematosus. Lupus 17:630–637CrossRefPubMedGoogle Scholar
  17. 17.
    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 171:803–810CrossRefGoogle Scholar
  18. 18.
    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 84:467–474CrossRefPubMedGoogle Scholar
  19. 19.
    Hanekom WA (2005) The immune response to BCG vaccination of newborns. Ann NY Acad Sci 1062:69–78CrossRefPubMedGoogle Scholar
  20. 20.
    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 128:199–204CrossRefPubMedGoogle Scholar
  21. 21.
    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 204:2159–2169CrossRefPubMedGoogle Scholar
  22. 22.
    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 30:130–132PubMedGoogle Scholar
  23. 23.
    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 179:1331–1339PubMedGoogle Scholar
  24. 24.
    Orme IM, Roberts AD, Griffin JP, Abrams JS (1993) Cytokine secretion by CD4 T lymphocytes acquired in response to Mycobacterium tuberculosis infection. J Immunol 151:518–525PubMedGoogle Scholar
  25. 25.
    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 148:189–196PubMedGoogle Scholar
  26. 26.
    Tran DQ, Shevach EM (2009) Therapeutic potential of FOXP3(+) regulatory T cells and their interactions with dendritic cells. Hum Immunol 70:294–299CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • X.-Y. He
    • 1
    Email author
  • L. Xiao
    • 1
  • H.-B. Chen
    • 2
  • J. Hao
    • 1
  • J. Li
    • 2
  • Y.-J. Wang
    • 1
  • K. He
    • 2
  • Y. Gao
    • 1
  • B.-Y. Shi
    • 1
  1. 1.Central Lab.The 309th Hospital of the Chinese People’s Liberation Army, ChinaBeijingChina
  2. 2.Tuberculosis InstituteThe 309th Hospital of the Chinese People’s Liberation Army, ChinaBeijingChina

Personalised recommendations