FoxP3+ regulatory T cells suppress effector T-cell function at pathologic site in miliary tuberculosis.
BACKGROUND
The inadequacy of effector T-cell response in containment of tubercle bacilli is believed to result in the development of disseminated forms of tuberculosis (TB), such as miliary tuberculosis (MTB). Regulatory T cells (Treg) plausibly play a critical role in the immunopathogenesis of disseminated TB by suppression of effector immune response against Mycobacterium tuberculosis at the pathologic site(s). To understand the role of Treg cells in disseminated tuberculosis, we studied the frequency and function of Treg cells derived from the local disease site specimens (LDSS) of patients with TB pleural effusion and MTB as clinical models of contained and disseminated forms of disease, respectively.


OBJECTIVE
To (1) enumerate the frequency of Treg cells in bronchoalveolar lavage (BAL) fluid of patients with MTB and compare with that of peripheral blood, (2) study the role of Treg cells in suppression of local T-cell response, and (3) study the selective recruitment of Treg cells at the local disease site(s).


METHODS
Flow cytometry, reverse transcriptase polymerase chain reaction, and 3-(4,5-dimethylthythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT)-based cell proliferation assay.


RESULTS
Frequency of Treg cells (CD4(+)CD25(+)FoxP3(+)) was significantly higher in LDSS in MTB along with higher levels of FoxP3 mRNA. Importantly, FoxP3(+) Treg cells obtained from the BAL of patients with MTB predominantly produced IL-10 and could suppress the autologous T-cell proliferation in response to M. tuberculosis antigen.


CONCLUSIONS
Our results highlight the importance of Treg cells in suppression of effector immune response and their influence on bacillary dissemination, disease manifestation, and severity.
Sharma
Prabhat K
PK
Department of Transplant Immunology and Immunogenetics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India.
Saha
Pradip K
PK
Singh
Amar
A
Sharma
Surendra K
SK
Ghosh
Balaram
B
Mitra
Dipendra K
DK
D000293:Adolescent; D000328:Adult; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology*; D016022:Case-Control Studies; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D016867:Immunocompromised Host / Q000276:immunology*; D016753:Interleukin-10 / Q000378:metabolism; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D010996:Pleural Effusion / Q000276:immunology* / Q000382:microbiology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000378:metabolism; D014391:Tuberculosis, Miliary / Q000276:immunology* / Q000503:physiopathology; D055815:Young Adult
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508609:IL10 protein, human; D016753:Interleukin-10