Document Detail

Different immunosuppressive mechanisms in multi-drug-resistant tuberculosis and non-tuberculous mycobacteria patients.
MedLine Citation:
PMID:  23286948     Owner:  NLM     Status:  MEDLINE    
Previous studies have demonstrated that cells from both multi-drug-resistant tuberculosis (MDR-TB) and non-tuberculous mycobacteria (NTM) patients respond poorly to mycobacterial antigens in vitro. In the present study, we compared the in vitro response of cells isolated from sensitive TB (NR-TB)-, MDR-TB- and NTM-infected patients. Analysis of T cell phenotype ex vivo revealed that both MDR-TB and NTM patients present an increased percentage of CD4(+) CD25(+-) forkhead box protein 3 (FoxP3)(+) and CD4(+) CD25(+) CD127(-) regulatory T (T(reg) ) cells when compared to NR-TB. Increased numbers of T(reg) cells and interleukin (IL)-10 serum levels were detected in MDR-TB, whereas elevated serum transforming growth factor (TGF)-β was found in the NTM group. Cells of MDR-TB patients stimulated with early secretory antigenic target (ESAT)-6, but not purified protein derivative (PPD), showed a lower frequency of CD4(+) /interferon (IFN)-γ(+) T cells and enhanced CD4(+) CD25(+) FoxP3(+) , CD4(+) CD25(+) CD127(-) and CD4(+) CD25(+) IL-10(+) T cell population. In addition, increased IL-10 secretion was observed in cultured MDR-TB cells following ESAT-6 stimulation, but not in NR-TB or NTM patients. In vitro blockade of IL-10 or IL-10Rα decreased the CD4(+) CD25(+) FoxP3(+) frequencies induced by ESAT-6 in MDR-TB, suggesting a role of IL-10 on impaired IFN-γ responses seen in MDR-TB. Depletion of CD4(+) CD25(+) T lymphocytes restored the capacity of MDR-TB T cells to respond to ESAT-6 in vitro, which suggests a potential role for T(reg) /T regulatory 1 cells in the pathogenesis of MDR-TB. Together, our results indicate that although the similarities in chronicity, NTM- and MDR-TB-impaired antigenic responses involve different mechanisms.
R O Pinheiro; E B de Oliveira; G Dos Santos; G M Sperandio da Silva; B J de Andrade Silva; R M B Teles; A Milagres; E N Sarno; M P Dalcolmo; E P Sampaio
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Clinical and experimental immunology     Volume:  171     ISSN:  1365-2249     ISO Abbreviation:  Clin. Exp. Immunol.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-04     Completed Date:  2013-03-12     Revised Date:  2014-02-04    
Medline Journal Info:
Nlm Unique ID:  0057202     Medline TA:  Clin Exp Immunol     Country:  England    
Other Details:
Languages:  eng     Pagination:  210-9     Citation Subset:  IM    
Copyright Information:
© 2012 British Society for Immunology.
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MeSH Terms
Antigens, Bacterial / immunology
Antigens, CD / metabolism
Bacterial Proteins / immunology
Cells, Cultured
Cytokines / immunology
Forkhead Transcription Factors / metabolism
Immune Tolerance*
Isoniazid / therapeutic use
Middle Aged
Rifampin / therapeutic use
T-Lymphocyte Subsets / drug effects,  immunology*
T-Lymphocytes, Regulatory / drug effects,  immunology*
Tuberculosis, Multidrug-Resistant / immunology*
Tuberculosis, Pulmonary / drug therapy,  immunology*,  microbiology
Young Adult
Reg. No./Substance:
0/Antigens, Bacterial; 0/Antigens, CD; 0/Bacterial Proteins; 0/Cytokines; 0/ESAT-6 protein, Mycobacterium tuberculosis; 0/FOXP3 protein, human; 0/Forkhead Transcription Factors; V83O1VOZ8L/Isoniazid; VJT6J7R4TR/Rifampin

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