Effective expansion of forkhead box P3+ regulatory T cells via early secreted antigenic target 6 and antigen 85 complex B from Mycobacterium tuberculosis

Wu,Ying‑E; Du,Zhong‑Ren; Cai,Ying‑Mu; Peng,Wen‑Guang; Zheng,Gao‑Zhe; Zheng,Geng‑Long; Wu,Li‑Biao; Li,Ke

doi:10.3892/mmr.2014.3033

Effective expansion of forkhead box P3+ regulatory T cells via early secreted antigenic target 6 and antigen 85 complex B from Mycobacterium tuberculosis

Authors:
- Ying‑E Wu
- Zhong‑Ren Du
- Ying‑Mu Cai
- Wen‑Guang Peng
- Gao‑Zhe Zheng
- Geng‑Long Zheng
- Li‑Biao Wu
- Ke Li
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Affiliations: Department of Laboratory Medicine, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, P.R. China, Information Department, Fengtai Center for Disease Control and Prevention, Beijing 100013, P.R. China, Department of Chest Surgery, The Third People's Hospital of Shantou City, Shantou, Guangdong 515041, P.R. China, Guangdong Key Laboratory of Medical Molecular Imaging, Shantou University Medical College, Shantou, Guangdong 515031, P.R. China, Laboratory of Molecular Cardiology, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, P.R. China, Department of Preventive Medicine, Shantou University Medical College, Shantou, Guangdong 515031, P.R. China
Published online on: December 3, 2014 https://doi.org/10.3892/mmr.2014.3033
Pages: 3134-3142

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Abstract

The expansion of CD4+ CD25+ forkhead box (FOX)P3+ regulatory T (Treg) cells has been observed in patients with Mycobacterium (M.) tuberculosis; however, the mechanism of expansion remains to be elucidated. The aim of the present study was to examine the role of the early secreted antigenic target 6(ESAT‑6) and antigen 85 complex B (Ag85B) from M. tuberculosis on Treg cell expansion. To investigate the sensitivity of peripheral blood cultures to the M. tuberculosis ESAT‑6 and Ag85B antigens, the proportion of circulating CD4+ CD25+ FOXP3+ Treg cells was determined using flow cytometry and the levels of FOXP3 mRNA were determined using reverse transcription quantitative polymerase chain reaction. The mRNA levels of FOXP3 and the proportion of circulating CD4+ CD25+ FOXP3+ Treg cells were increased in multiplicitous drug‑resistant tuberculosis patients compared with those in healthy controls and patients with latent tuberculosis (TB) infection (LTBI) (P<0.001). The mycobacterial antigens ESAT‑6 and Ag85B increased the expansion of the CD4+ CD25+ FOXP3+ Treg cells and the mRNA levels of FOXP3 in healthy controls and LTBI patients compared with the effect of Bacillus Calmette‑Guerin (P<0.05). Additionally, the mRNA levels of FOXP3 were elevated in the LTBI patients following stimulations with the mycobacterial antigens (P=0.012). Therefore, the M. tuberculosis antigens ESAT‑6 and Ag85B induced CD4+ CD25+ FOXP3+ Treg‑cell expansion, particularly in patients with LTBI. These findings indicated that CD4+ CD25+ FOXP3+ Treg cells may have a primary role in the failure of the host immune system to eradicate M. tuberculosis.

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