title: Effective expansion of forkhead box P3⁺ regulatory T cells via early secreted antigenic target 6 and antigen 85 complex B from Mycobacterium tuberculosis.
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.
authors.affiliation: Department of Laboratory Medicine, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, P.R. China.
authors.forename: Ying-E
authors.initials: YE
authors.lastname: Wu
authors.affiliation: Information Department, Fengtai Center for Disease Control and Prevention, Beijing 100013, P.R. China.
authors.forename: Zhong-Ren
authors.initials: ZR
authors.lastname: Du
authors.affiliation: Department of Laboratory Medicine, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, P.R. China.
authors.forename: Ying-Mu
authors.initials: YM
authors.lastname: Cai
authors.affiliation: Department of Chest Surgery, The Third People's Hospital of Shantou City, Shantou, Guangdong 515041, P.R. China.
authors.forename: Wen-Guang
authors.initials: WG
authors.lastname: Peng
authors.affiliation: Department of Laboratory Medicine, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, P.R. China.
authors.forename: Gao-Zhe
authors.initials: GZ
authors.lastname: Zheng
authors.affiliation: Guangdong Key Laboratory of Medical Molecular Imaging, Shantou University Medical College, Shantou, Guangdong 515031, P.R. China.
authors.forename: Geng-Long
authors.initials: GL
authors.lastname: Zheng
authors.affiliation: Laboratory of Molecular Cardiology, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, P.R. China.
authors.forename: Li-Biao
authors.initials: LB
authors.lastname: Wu
authors.affiliation: Department of Preventive Medicine, Shantou University Medical College, Shantou, Guangdong 515031, P.R. China.
authors.forename: Ke
authors.initials: K
authors.lastname: Li
mesh_terms: D000217:Acyltransferases / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D018791:CD4 Lymphocyte Count; D016022:Case-Control Studies; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D016130:Immunophenotyping; D055985:Latent Tuberculosis / Q000235:genetics / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism*; D014376:Tuberculosis / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D018088:Tuberculosis, Multidrug-Resistant / Q000235:genetics / Q000276:immunology; D055815:Young Adult
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C093276:ESAT-6 protein, Mycobacterium tuberculosis; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger; D000217:Acyltransferases; C121433:antigen 85B, Mycobacterium tuberculosis