Early Dynamics of T Helper Cell Cytokines and T Regulatory Cells in Response to Treatment of Active Mycobacterium Tuberculosis Infection

Overview

Journal Clin Exp Immunol

Publisher Oxford University Press

Specialty Allergy & Immunology

Date 2014 Oct 15

PMID 25313008

Citations 28

Authors

S L Feruglio

K Tonby

D Kvale

A M Dyrhol-Riise

Affiliations

Soon will be listed here.

Abstract

Biomarkers that can identify tuberculosis (TB) disease and serve as markers for efficient therapy are requested. We have studied T cell cytokine production [interferon (IFN)-γ, interleukin (IL)-2, tumour necrosis factor (TNF)-α] and degranulation (CD107a) as well as subsets of CD4(+) T regulatory cells (Tregs ) after in-vitro Mycobacterium tuberculosis (Mtb) antigen stimulation [early secretory antigenic target (ESAT)-6, culture filtrate protein (CFP)-10, antigen 85 (Ag85)] in 32 patients with active tuberculosis (TB) disease throughout 24 weeks of effective TB treatment. A significant decline in the fraction of Mtb-specific total IFN-γ and single IFN-γ-producing T cells was already observed after 2 weeks of treatment, whereas the pool of single IL-2(+) cells increased over time for both CD4(+) and CD8(+) T cells. The Treg subsets CD25(high) CD127(low) , CD25(high) CD147(++) and CD25(high) CD127(low) CD161(+) expanded significantly after Mtb antigen stimulation in vitro at all time-points, whereas the CD25(high) CD127(low) CD39(+) Tregs remained unchanged. The fraction of CD25(high) CD127(low) Tregs increased after 8 weeks of treatment. Thus, we revealed an opposing shift of Tregs and intracellular cytokine production during treatment. This may indicate that functional signatures of the CD4(+) and CD8(+) T cells can serve as immunological correlates of early curative host responses. Whether such signatures can be used as biomarkers in monitoring and follow-up of TB treatment needs to be explored further.

Citing Articles

Identifying the Interaction Between Tuberculosis and SARS-CoV-2 Infections via Bioinformatics Analysis and Machine Learning.

Huang Z, Kang J, Chen P, Deng L, Li J, He Y Biochem Genet. 2023; 62(4):2606-2630.

PMID: 37991568 DOI: 10.1007/s10528-023-10563-x.

New Insights into Biomarkers for Evaluating Therapy Efficacy in Pulmonary Tuberculosis: A Narrative Review.

Zhang F, Zhang F, Dong Y, Li L, Pang Y Infect Dis Ther. 2023; 12(12):2665-2689.

PMID: 37938418 PMC: 10746651. DOI: 10.1007/s40121-023-00887-x.

Helper T cell bias following tuberculosis chemotherapy identifies opportunities for therapeutic vaccination to prevent relapse.

Martinez-Martinez Y, Huante M, Chauhan S, Naqvi K, Bharaj P, Endsley J NPJ Vaccines. 2023; 8(1):165.

PMID: 37898618 PMC: 10613213. DOI: 10.1038/s41541-023-00761-4.

A united model for diagnosing pulmonary tuberculosis with random forest and artificial neural network.

Zhu Q, Liu J Front Genet. 2023; 14:1094099.

PMID: 36968608 PMC: 10033863. DOI: 10.3389/fgene.2023.1094099.

Identification and validation of a T-cell-related MIR600HG/hsa-mir-21-5p competing endogenous RNA network in tuberculosis activation based on integrated bioinformatics approaches.

Hong G, Guan Q, Peng H, Luo X, Mao Q Front Genet. 2022; 13:979213.

PMID: 36204312 PMC: 9531151. DOI: 10.3389/fgene.2022.979213.

References

Young J, Adetifa I, Ota M, Sutherland J . Expanded polyfunctional T cell response to mycobacterial antigens in TB disease and contraction post-treatment. PLoS One. 2010; 5(6):e11237. PMC: 2888639. DOI: 10.1371/journal.pone.0011237. View

Roederer M, Nozzi J, Nason M . SPICE: exploration and analysis of post-cytometric complex multivariate datasets. Cytometry A. 2011; 79(2):167-74. PMC: 3072288. DOI: 10.1002/cyto.a.21015. View

Ottenhoff T . New pathways of protective and pathological host defense to mycobacteria. Trends Microbiol. 2012; 20(9):419-28. DOI: 10.1016/j.tim.2012.06.002. View

de Almeida A, Fiske C, Sterling T, Kalams S . Increased frequency of regulatory T cells and T lymphocyte activation in persons with previously treated extrapulmonary tuberculosis. Clin Vaccine Immunol. 2011; 19(1):45-52. PMC: 3255960. DOI: 10.1128/CVI.05263-11. View

Djoba Siawaya J, Beyers N, van Helden P, Walzl G . Differential cytokine secretion and early treatment response in patients with pulmonary tuberculosis. Clin Exp Immunol. 2009; 156(1):69-77. PMC: 2673743. DOI: 10.1111/j.1365-2249.2009.03875.x. View

Harari A, Rozot V, Bellutti Enders F, Perreau M, Mazza Stalder J, Nicod L . Dominant TNF-α+ Mycobacterium tuberculosis-specific CD4+ T cell responses discriminate between latent infection and active disease. Nat Med. 2011; 17(3):372-6. PMC: 6570988. DOI: 10.1038/nm.2299. View

Chiacchio T, Petruccioli E, Vanini V, Butera O, Cuzzi G, Petrone L . Higher frequency of T-cell response to M. tuberculosis latency antigen Rv2628 at the site of active tuberculosis disease than in peripheral blood. PLoS One. 2011; 6(11):e27539. PMC: 3213161. DOI: 10.1371/journal.pone.0027539. View

Chen X, Zhou B, Li M, Deng Q, Wu X, Le X . CD4(+)CD25(+)FoxP3(+) regulatory T cells suppress Mycobacterium tuberculosis immunity in patients with active disease. Clin Immunol. 2007; 123(1):50-9. DOI: 10.1016/j.clim.2006.11.009. View

Liu W, Putnam A, Xu-Yu Z, Szot G, Lee M, Zhu S . CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells. J Exp Med. 2006; 203(7):1701-11. PMC: 2118339. DOI: 10.1084/jem.20060772. View

10.

Lamoreaux L, Roederer M, Koup R . Intracellular cytokine optimization and standard operating procedure. Nat Protoc. 2007; 1(3):1507-16. DOI: 10.1038/nprot.2006.268. View

11.

Chiacchio T, Casetti R, Butera O, Vanini V, Carrara S, Girardi E . Characterization of regulatory T cells identified as CD4(+)CD25(high)CD39(+) in patients with active tuberculosis. Clin Exp Immunol. 2009; 156(3):463-70. PMC: 2691975. DOI: 10.1111/j.1365-2249.2009.03908.x. View

12.

OGarra A, Redford P, McNab F, Bloom C, Wilkinson R, Berry M . The immune response in tuberculosis. Annu Rev Immunol. 2013; 31:475-527. DOI: 10.1146/annurev-immunol-032712-095939. View

13.

den Hertog A, de Vos A, Klatser P, Anthony R . Early specific host response associated with starting effective tuberculosis treatment in an infection controlled placebo controlled mouse study. PLoS One. 2013; 8(2):e57997. PMC: 3585278. DOI: 10.1371/journal.pone.0057997. View

14.

Chiappini E, Fossi F, Bonsignori F, Sollai S, Galli L, de Martino M . Utility of interferon-γ release assay results to monitor anti-tubercular treatment in adults and children. Clin Ther. 2012; 34(5):1041-8. DOI: 10.1016/j.clinthera.2012.03.006. View

15.

He X, Xiao L, Chen H, Hao J, Li J, Wang Y . T regulatory cells and Th1/Th2 cytokines in peripheral blood from tuberculosis patients. Eur J Clin Microbiol Infect Dis. 2010; 29(6):643-50. DOI: 10.1007/s10096-010-0908-0. View

16.

Harris J, Keane J . How tumour necrosis factor blockers interfere with tuberculosis immunity. Clin Exp Immunol. 2010; 161(1):1-9. PMC: 2940142. DOI: 10.1111/j.1365-2249.2010.04146.x. View

17.

Mattos A, Almeida C, Franken K, Alves C, Abramo C, de Souza M . Increased IgG1, IFN-gamma, TNF-alpha and IL-6 responses to Mycobacterium tuberculosis antigens in patients with tuberculosis are lower after chemotherapy. Int Immunol. 2010; 22(9):775-82. DOI: 10.1093/intimm/dxq429. View

18.

Shafiani S, Dinh C, Ertelt J, Moguche A, Siddiqui I, Smigiel K . Pathogen-specific Treg cells expand early during mycobacterium tuberculosis infection but are later eliminated in response to Interleukin-12. Immunity. 2013; 38(6):1261-70. PMC: 3827956. DOI: 10.1016/j.immuni.2013.06.003. View

19.

Marin N, Paris S, Velez V, Rojas C, Rojas M, Garcia L . Regulatory T cell frequency and modulation of IFN-gamma and IL-17 in active and latent tuberculosis. Tuberculosis (Edinb). 2010; 90(4):252-61. DOI: 10.1016/j.tube.2010.05.003. View

20.

Sester U, Fousse M, Dirks J, Mack U, Prasse A, Singh M . Whole-blood flow-cytometric analysis of antigen-specific CD4 T-cell cytokine profiles distinguishes active tuberculosis from non-active states. PLoS One. 2011; 6(3):e17813. PMC: 3058054. DOI: 10.1371/journal.pone.0017813. View