Depressed T-cell interferon-gamma responses in pulmonary tuberculosis: Analysis of underlying mechanisms and modulation with therapy

Immunological and clinical profiles were evaluated in 2 groups: human immun odeficiency virus (HIV)-uninfected and HIV-infected patients, with newly di agnosed pulmonary tuberculosis (TB), and tuberculin-skin-test-reactive heal thy control subjects. HIV-uninfected patients with TB were also followed up longitudinally during and after chemotherapy, At the time of diagnosis, pu rified protein derivative (PPD)-stimulated production of interferon (IFN)-g amma by peripheral blood mononuclear cells from TB patients was depressed, compared with that of healthy control subjects, whereas levels of transform ing growth factor (TGF)-beta and interleukin (IL)-10 were increased. In lon gitudinal studies, PPD stimulated production of IL-10 and TGF-beta returned to baseline by 3 months, whereas IFN-gamma production remained depressed f or at least 12 months. These data indicate that the immunosuppression of TB is not only immediate and apparently dependent (at least in part) on immun osuppressive cytokines early during the course of Mycobacterium TB infectio n but is also long lasting, presumably relating to a primary abnormality in T-cell function.