title: Changes in the kinetics of intracellular IFN-gamma production in TB patients during treatment.
abstract: The role of T lymphocyte cytokine responses in tuberculosis (TB) still needs clarification. This study aimed to define interferon-gamma (IFN-gamma) responses longitudinally in HIV-negative TB patients during treatment, compared to those of healthy volunteers. Flow cytometric intracellular IFN-gamma determinations after CD3 stimulation were done in parallel with lymphocyte proliferation assays in response to mycobacterial antigen. Percentages of IFN-gamma-producing CD8 and CD4 T lymphocytes in patients at diagnosis were significantly higher than in controls but normalized during treatment. Additional kinetic studies suggested accelerated IFN-gamma production in patients at diagnosis, compared to controls and treated patients. Lymphocyte proliferation was below normal in patients at diagnosis and increased rapidly with decreasing bacterial load during treatment. We conclude that T cell IFN-gamma response kinetics in TB patients suggest a pre-activated state at diagnosis, which changes during treatment. At diagnosis intracellular IFN-gamma or lymphocyte proliferation was not an indicator for treatment response.
authors.affiliation: Division of Molecular Biology and Human Genetics, MRC Centre for Molecular and Cellular Biology and the DST/NRF Centre of Excellence for Biomedical TB Research, University of Stellenbosch, PO Box 19063, 7505 Tygerberg, South Africa. hveen@sun.ac.za
authors.forename: Hanne
authors.initials: H
authors.lastname: Veenstra
authors.forename: Ilse
authors.initials: I
authors.lastname: Crous
authors.forename: Shweta
authors.initials: S
authors.lastname: Brahmbhatt
authors.forename: Pauline
authors.initials: P
authors.lastname: Lukey
authors.forename: Nulda
authors.initials: N
authors.lastname: Beyers
authors.forename: Paul D
authors.initials: PD
authors.lastname: van Helden
authors.forename: Gerhard
authors.initials: G
authors.lastname: Walzl
mesh_terms: D000293:Adolescent; D000328:Adult; D017252:CD3 Complex / Q000494:pharmacology*; D016516:CD4-CD8 Ratio; D049109:Cell Proliferation; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000097:blood / Q000378:metabolism*; D007700:Kinetics; D008137:Longitudinal Studies; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009165:Mycobacterium Infections, Nontuberculous / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy / Q000276:immunology*
chemical_list: D017252:CD3 Complex; D007371:Interferon-gamma