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

Sauzullo I, Mengoni F, Lichtner M, Massetti AP, Rossi R, Iannetta M, Marocco R, Del Borgo C, Soscia F, Vullo V, Mastroianni CM - PLoS ONE (2009)

Bottom Line: 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.In addition, the antituberculous drugs do not have any direct down-regulatory effect on the specific IFN-gamma response.

View Article: PubMed Central - PubMed

Affiliation: Department of Infectious and Tropical Diseases, Sapienza University, Rome, Italy.

ABSTRACT

Background: 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.

Principal findings: 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.

Conclusions: 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.

Show MeSH

Related in: MedlinePlus

Cytofluorimetric analysis of phenotypic profile of T cells from two representative TB patients at the end of treatment.A representative sample of one TB patient with QFT-G reversion (positive to negative) at the end of therapy (panel A) and one TB patient with persistent QFT-G positive result (panel B) is shown. The percentage of CD4+ and CD8+ T cells that expressed CD45RO and lymphotropic chemokine receptor CCR7 was assessed in diluted whole blood after 6 days of in vitro stimulation with intact recombinant ESAT-6 and CFP-10 proteins. Effector memory (EM) cells (CD45RO+/CCR7−) are shown in the upper left quadrants of both panels; central/memory (CM) cells (CD45RO+/CCR7+) are showed in the upper right quadrants of both panels.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2664463&req=5

pone-0005187-g003: Cytofluorimetric analysis of phenotypic profile of T cells from two representative TB patients at the end of treatment.A representative sample of one TB patient with QFT-G reversion (positive to negative) at the end of therapy (panel A) and one TB patient with persistent QFT-G positive result (panel B) is shown. The percentage of CD4+ and CD8+ T cells that expressed CD45RO and lymphotropic chemokine receptor CCR7 was assessed in diluted whole blood after 6 days of in vitro stimulation with intact recombinant ESAT-6 and CFP-10 proteins. Effector memory (EM) cells (CD45RO+/CCR7−) are shown in the upper left quadrants of both panels; central/memory (CM) cells (CD45RO+/CCR7+) are showed in the upper right quadrants of both panels.

Mentions: Similarly, the percentage of CD8+T-cells with EM phenotype was significantly higher in patients with positive QFT-G results than in those with negative QFT-G results (p = 0.036 for EM). No significant difference was observed in the percentage of CD8+ T-cells with CM phenotype among two groups of patients (p = 0.087) (Table 5). The cytofluorimetric analysis from a representative TB patient with QFT-G reversion (positive to negative) and a patient with persistent QFT-G positive after treatment is shown in Figure 3.


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

Sauzullo I, Mengoni F, Lichtner M, Massetti AP, Rossi R, Iannetta M, Marocco R, Del Borgo C, Soscia F, Vullo V, Mastroianni CM - PLoS ONE (2009)

Cytofluorimetric analysis of phenotypic profile of T cells from two representative TB patients at the end of treatment.A representative sample of one TB patient with QFT-G reversion (positive to negative) at the end of therapy (panel A) and one TB patient with persistent QFT-G positive result (panel B) is shown. The percentage of CD4+ and CD8+ T cells that expressed CD45RO and lymphotropic chemokine receptor CCR7 was assessed in diluted whole blood after 6 days of in vitro stimulation with intact recombinant ESAT-6 and CFP-10 proteins. Effector memory (EM) cells (CD45RO+/CCR7−) are shown in the upper left quadrants of both panels; central/memory (CM) cells (CD45RO+/CCR7+) are showed in the upper right quadrants of both panels.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2664463&req=5

pone-0005187-g003: Cytofluorimetric analysis of phenotypic profile of T cells from two representative TB patients at the end of treatment.A representative sample of one TB patient with QFT-G reversion (positive to negative) at the end of therapy (panel A) and one TB patient with persistent QFT-G positive result (panel B) is shown. The percentage of CD4+ and CD8+ T cells that expressed CD45RO and lymphotropic chemokine receptor CCR7 was assessed in diluted whole blood after 6 days of in vitro stimulation with intact recombinant ESAT-6 and CFP-10 proteins. Effector memory (EM) cells (CD45RO+/CCR7−) are shown in the upper left quadrants of both panels; central/memory (CM) cells (CD45RO+/CCR7+) are showed in the upper right quadrants of both panels.
Mentions: Similarly, the percentage of CD8+T-cells with EM phenotype was significantly higher in patients with positive QFT-G results than in those with negative QFT-G results (p = 0.036 for EM). No significant difference was observed in the percentage of CD8+ T-cells with CM phenotype among two groups of patients (p = 0.087) (Table 5). The cytofluorimetric analysis from a representative TB patient with QFT-G reversion (positive to negative) and a patient with persistent QFT-G positive after treatment is shown in Figure 3.

Bottom Line: 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.In addition, the antituberculous drugs do not have any direct down-regulatory effect on the specific IFN-gamma response.

View Article: PubMed Central - PubMed

Affiliation: Department of Infectious and Tropical Diseases, Sapienza University, Rome, Italy.

ABSTRACT

Background: 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.

Principal findings: 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.

Conclusions: 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.

Show MeSH
Related in: MedlinePlus