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

Christina S. Hirsch, Zahra Toossi, Catherine Othieno, John L. Johnson, Stephan K. Schwander, Steven Robertson, Robert S. Wallis, Kay Edmonds, Alphonse Okwera, Roy Mugerwa, Pierre Peters, Jerrold J. Ellner

Research output: Contribution to journalArticlepeer-review

240 Scopus citations

Abstract

Immunological and clinical profiles were evaluated in 2 groups: human immunodeficiency virus (HIV)-uninfected and HIV-infected patients, with newly diagnosed pulmonary tuberculosis (TB), and tuberculin-skin-test-reactive healthy control subjects. HIV-uninfected patients with TB were also followed up longitudinally during and after chemotherapy. At the time of diagnosis, purified protein derivative (PPD)-stimulated production of interferon (IFN)- γ by peripheral blood mononuclear cells from TB patients was depressed, compared with that of healthy control subjects, whereas levels of transforming growth factor (TGF)-β and interleukin (IL)-10 were increased. In longitudinal studies, PPD stimulated production of IL-10 and TGF-β returned to baseline by 3 months, whereas IFN-γ production remained depressed for at least 12 months. These data indicate that the immunosuppression of TB is not only immediate and apparently dependent (at least in part) on immunosuppressive cytokines early during the course of Mycobacterium TB infection but is also long lasting, presumably relating to a primary abnormality in T-cell function.

Original languageEnglish (US)
Pages (from-to)2069-2073
Number of pages5
JournalJournal of Infectious Diseases
Volume180
Issue number6
DOIs
StatePublished - 1999
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Infectious Diseases

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