Augmentation of Apoptosis and Interferon-γ Production at Sites of Active Mycobacterium tuberculosis Infection in Human Tuberculosis

• Published in: The Journal of infectious diseases 2001-03, Vol.183 (5), p.779-788
• Main Authors: Hirsch, C. S., Toossi, Z., Johnson, J. L., Luzze, H., Ntambi, L., Peters, P., McHugh, M., Okwera, A., Joloba, M., Mugyenyi, P., Mugerwa, R. D., Terebuh, P., Ellner, J. J.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; AIDS-Related Opportunistic Infections - blood; AIDS-Related Opportunistic Infections - immunology; AIDS-Related Opportunistic Infections - virology; Apoptosis; Apoptosis - immunology; Bacterial diseases; Biological and medical sciences; Blood plasma; CD4 antigen; CD4 Lymphocyte Count; Cells, Cultured; Cultured cells; Cytokines; Fas Ligand Protein; Female; g-Interferon; HIV; Human bacterial diseases; Human immunodeficiency virus; Human viral diseases; Humans; Infections; Infectious diseases; Interferon-gamma - biosynthesis; Interferon-gamma - immunology; Leukocytes, Mononuclear; Macrophages; Major Articles; Male; Medical sciences; Membrane Glycoproteins - analysis; Middle Aged; Mycobacterium tuberculosis; Mycobacterium tuberculosis - immunology; Mycobacterium tuberculosis - virology; Pleural tuberculosis; Pulmonary tuberculosis; T lymphocytes; T-Lymphocytes - cytology; T-Lymphocytes - immunology; Tuberculosis and atypical mycobacterial infections; Tuberculosis, Pleural - blood; Tuberculosis, Pleural - immunology; Tuberculosis, Pleural - virology; Tumor Necrosis Factor-alpha - analysis; Uganda; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/318817

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)–γ levels were increased in pleural fluid, compared with plasma. Spontaneous apoptosis correlated with specific loss of MTB-reactive, IFN-γ–producing pleural T cells. Immunoreactivities of molecules potentially involved in apoptosis, such as tumor necrosis factor–α, 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