Restoration of mycobacterial antigen-induced proliferation and interferon-γ responses in peripheral blood mononuclear cells of tuberculosis patients upon effective chemotherapy

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Abstract
Peripheral blood mononuclear cells (PBMC) were obtained from culture-proven tuberculosis (TB) patients before and after 2 and 6 months of chemotherapy with a multi-drug regimen. PBMC were tested for cellular responses in antigen-induced proliferation and interferon-γ (IFN-γ) assays in response to complex mycobacterial antigens (whole cell Mycobacterium bovis BCG and M. tuberculosis, cell walls and short-term culture filtrate [ST-CF] of M. tuberculosis), fractionated ST-CF antigens (fractions F1–F10) and ESAT-6. The responses in TB patients before anti-TB treatment were low (median stimulation index (SI)=1–7, median delta IFN-γ=0–12 U ml−1, and percent responders=13–67%) to all the antigenic preparations. Following the administration of anti-TB chemotherapy for 2 months, there were significant (P0.05, 100% responders). A further increase in IFN-γ responses (median delta IFN-γ=14–250 U ml−1 and percent responders=43–100%) to mycobacterial antigens was observed in patients receiving chemotherapy for 6 months. Among the ST-CF fractions, F1 and F2 containing low molecular mass proteins resulted in the highest responses, whereas ESAT-6 showed responses comparable to these fractions only in a minority of the patients. HLA-DR typing of these patients showed heterogeneity in the expression of molecules encoded by HLA-DRB genes. These results show that effective chemotherapy restores cellular responses of TB patients to a large number of M. tuberculosis antigens, which could be useful in monitoring the efficacy of anti-TB treatment.