title: Restoration of mycobacterial antigen-induced proliferation and interferon-gamma responses in peripheral blood mononuclear cells of tuberculosis patients upon effective chemotherapy.
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-gamma (IFN-gamma) 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-gamma=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-gamma=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-gamma responses (median delta IFN-gamma=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.
authors.affiliation: Department of Microbiology, Faculty of Medicine, Kuwait University, PO Box 24923, 13110 Safat, Kuwait. rj-alattiyah@hsc.kuniv.edu.kw
authors.forename: R
authors.initials: R
authors.lastname: Al-Attiyah
authors.forename: A S
authors.initials: AS
authors.lastname: Mustafa
authors.forename: A T
authors.initials: AT
authors.lastname: Abal
authors.forename: N M
authors.initials: NM
authors.lastname: Madi
authors.forename: P
authors.initials: P
authors.lastname: Andersen
mesh_terms: D000942:Antigens, Bacterial / Q000276:immunology*; D000995:Antitubercular Agents / Q000627:therapeutic use; D002455:Cell Division; D003208:Concanavalin A / Q000494:pharmacology; D004359:Drug Therapy, Combination; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D009161:Mycobacterium / Q000276:immunology*; D009163:Mycobacterium bovis / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D014376:Tuberculosis / Q000097:blood / Q000188:drug therapy* / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D000995:Antitubercular Agents; D006684:HLA-DR Antigens; D003208:Concanavalin A; D007371:Interferon-gamma