Pleural tuberculosis (TB) was employed as a model to study T cell apoptosis at sites of active Mycobacterium tuberculosis (MTB) infection in human immunodeficiency virus (HIV)-coinfected (HIV/TB) patients and patients infected with TB alone. Apoptosis in blood and in pleural fluid mononuclear cells and cytokine immunoreactivities in plasma and in pleural fluid were evaluated. T cells were expanded at the site of MTB infection, irrespective of HIV status. Apoptosis of CD4 and non-CD4 T cells in the pleural space occurred in both HIV/TB and TB. Interferon (IFN)-gamma levels were increased in pleural fluid, compared with plasma. Spontaneous apoptosis correlated with specific loss of MTB-reactive, IFN-gamma-producing pleural T cells. Immunoreactivities of molecules potentially involved in apoptosis, such as tumor necrosis factor-alpha, Fas-ligand, and Fas, were increased in pleural fluid, compared with plasma. These data suggest that continued exposure of immunoreactive cells to MTB at sites of infection may initiate a vicious cycle in which immune activation and loss of antigen-responsive T cells occur concomitantly, thus favoring persistence of MTB infection.

Immune parameters were compared in four groups of Ugandan subjects: HIV−and HIV+ adult patients with active pulmonary TB (HIV− PTB n = 38; HIV+ PTB n = 28), patients with HIV infection only (n = 26) and PPD+ healthy controls (n = 25). Compared with healthy controls, CD4 and CD8 T cells from patients with HIV and/or PTB expressed more activation markers (HLA‐DR, CD38); their CD8 T cells expressed more CD95 (pre‐apoptosis) and less CD28 (co‐stimulatory receptor). Peripheral blood mononuclear cells (PBMC) of patients with either HIV or PTB were impaired in interferon‐gamma (IFN‐γ) production upon antigenic stimulation. PTB (with or without HIV) was characterized by monocytosis, granulocytosis, increased transforming growth factor‐beta 1 production and PPD‐induced apoptosis. In vivo CD4 T cell depletion, in vitro increased spontaneous CD4 T cell apoptosis and defects in IFN‐γ responses upon mitogenic stimulation were restricted to HIV+ subjects (with or without PTB). Overlapping and distinctive immune alterations, associated with PTB and HIV, might explain mutual unfavourable influences of both diseases.