Cytokine–Producing CD4+ T Lymphocytes in the Lung: A Characteristic Feature of Active Pulmonary and Nonpulmonary Tuberculosis

Because tuberculosis (TB) is primarily a pulmonary disease, we examined the cytokine responses of CD4+ T lymphocytes in bronchoalveolar lavage (BAL) fluid after incubation with purified protein derivative (PPD) in human immunodeficiency virus–negative patients with TB and control subjects with nontuberculous respi-ratory disease. Parallel blood and BAL fluid samples from each subject were incubated with or without PPD, and the proportions of CD4+ T lymphocytes producing interferon (IFN)–g or tumor necrosis factor (TNF)–a were measured by flow cytometry. The proportions of PPD-activated IFN-g – and TNF-a–producing CD4+ cells were low among control subjects (median, 0.33 % and 0.78%, respectively). By contrast, among patients with TB, strong IFN-g and TNF-a responses were demonstrated (median, 24.0 % and 32.4%, respectively), regardless of whether the TB was pulmonary or nonpulmonary. Measurement of type 1 cytokine production by CD4+ T lymphocytes in response to PPD in BAL fluid is a promising new diagnostic test for active TB in immunocompetent individuals. It is estimated that one-third of the world’s population is infected with Mycobacterium tuberculosis and that there are 8 million new cases of tuberculosis (TB) and nearly 3 million TB-related deaths each year [1]. Th