In vivo and in vitro effects of antituberculosis treatment on mycobacterial interferon-gamma T cell response

In recent years, the impact of antituberculous treatment on interferon (IFN)-gamma response to Mycobacterium tuberculosis antigens has been widely investigated, but the results have been controversial. The objective of the present study was: i) to evaluate longitudinal changes of IFN-gamma response...

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Bibliographic Details
Published in:PloS one 2009-04, Vol.4 (4), p.e5187-e5187
Main Authors: Sauzullo, Ilaria, Mengoni, Fabio, Lichtner, Miriam, Massetti, Anna Paola, Rossi, Raffaella, Iannetta, Marco, Marocco, Raffaella, Del Borgo, Cosmo, Soscia, Fabrizio, Vullo, Vincenzo, Mastroianni, Claudio Maria
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Antigens
Antigens, Bacterial - immunology
Antitubercular Agents - immunology
Antitubercular Agents - therapeutic use
Blood & organ donations
CD4 antigen
CD4-Positive T-Lymphocytes - immunology
CD4-Positive T-Lymphocytes - secretion
CD8 antigen
CD8-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - secretion
Clinical medicine
Drugs
Effector cells
ESAT-6 antigen
Female
Humans
Immunological memory
Incubation
Infections
Infectious Diseases
Infectious Diseases/Bacterial Infections
Infectious Diseases/Respiratory Infections
Interferon
Interferon-gamma - immunology
Interferon-gamma - secretion
Lymphocytes
Lymphocytes T
Male
Memory cells
Mycobacterium tuberculosis
Mycobacterium tuberculosis - immunology
Patients
Pharmacology
Reversion
Skin
T cell receptors
Therapy
Tropical diseases
Tuberculosis
Tuberculosis - drug therapy
Tuberculosis - immunology
Young Adult
γ-Interferon
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Summary:In recent years, the impact of antituberculous treatment on interferon (IFN)-gamma response to Mycobacterium tuberculosis antigens has been widely investigated, but the results have been controversial. The objective of the present study was: i) to evaluate longitudinal changes of IFN-gamma response to M. tuberculosis-specific antigens in TB patients during antituberculous treatment by using the QuantiFERON-TB Gold (QFT-G) assay; ii) to compare the differences in T-cell response after a short or prolonged period of stimulation with mycobacterial antigens; iii) to assess the CD4+ and CD8+ T cells with effector/memory and central/memory phenotype; iv) to investigate the direct in vitro effects of antituberculous drugs on the secretion of IFN-gamma. 38 TB patients was evaluated at baseline and at month 2 and 4 of treatment and at month 6 (treatment completion). 27 (71%) patients had a QFT-G reversion (positive to negative) at the end of therapy, while 11 (29%) TB patients remained QFT-G positive at the end of therapy. Among the 11 patients with persistent positive QFT-G results, six had a complete response to the treatment, while the remaining 5 patients did not have a resolution of the disease. All 27 patients who became QFT-G negative had a complete clinical and microbiological recovery of the TB disease. In these patients the release of IFN-gamma is absent even after a prolonged 6-day incubation with both ESAT-6 and CFP-10 antigens and the percentage of effector/memory T-cells phenotype was markedly lower than subjects with persistent positive QFT-G results. The in vitro study showed that antituberculous drugs did not exert any inhibitory effect on IFN-gamma production within the range of therapeutically achievable concentrations. The present study suggests that the decrease in the M. tuberculosis-specific T cells responses following successful anti-TB therapy may have a clinical value as a supplemental tool for the monitoring of the efficacy of pharmacologic intervention for active TB. In addition, the antituberculous drugs do not have any direct down-regulatory effect on the specific IFN-gamma response.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0005187