Open AccessRestoration of mycobacterial antigen‐induced proliferation and interferon‐γ responses in peripheral blood mononuclear cells of tuberculosis patients upon effective chemotherapy
Author(s) -
AlAttiyah R,
Mustafa A.S,
Abal A.T,
Madi N.M,
Andersen P
Publication year - 2003
Publication title -
fems immunology & medical microbiology
Language(s) - English
Resource type - Journals
eISSN - 1574-695X
pISSN - 0928-8244
DOI - 10.1016/s0928-8244(03)00166-4
Subject(s) - peripheral blood mononuclear cell , tuberculosis , immunology , biology , antigen , interferon gamma , chemotherapy , interferon γ , mycobacterium tuberculosis , peripheral blood , interferon , virology , medicine , pathology , immune system , in vitro , biochemistry , genetics
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 ( P <0.05 ) improvements in the cellular responses (median SI=9–76, median delta IFN‐γ=3–70 U ml −1 , and percent responders=33–100%) to most of the antigenic preparations tested. However, concanavalin A‐induced proliferation responses of PBMC from the same patients before and after 2 months of chemotherapy were high and comparable (median SI=101 and 114, respectively, P >0.05 , 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.