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


RESULTS
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.
Department of Infectious and Tropical Diseases, Sapienza University, Rome, Italy.
Ilaria
I
Sauzullo
Fabio
F
Mengoni
Miriam
M
Lichtner
Anna Paola
AP
Massetti
Raffaella
R
Rossi
Marco
M
Iannetta
Raffaella
R
Marocco
Cosmo
C
Del Borgo
Fabrizio
F
Soscia
Vincenzo
V
Vullo
Claudio Maria
CM
Mastroianni
D000293:Adolescent; D000328:Adult; D000368:Aged; D000942:Antigens, Bacterial / Q000276:immunology; D000995:Antitubercular Agents / Q000276:immunology / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology* / Q000378:metabolism; D008297:Male; D009169:Mycobacterium tuberculosis / Q000276:immunology; D014376:Tuberculosis / Q000188:drug therapy / Q000276:immunology; D055815:Young Adult
D000942:Antigens, Bacterial; D000995:Antitubercular Agents; C072681:Mycobacterium tuberculosis antigens; D007371:Interferon-gamma