Augmentation of apoptosis and interferon-gamma production at sites of active Mycobacterium tuberculosis infection in human tuberculosis.

TitleAugmentation of apoptosis and interferon-gamma production at sites of active Mycobacterium tuberculosis infection in human tuberculosis.
Publication TypeJournal Article
Year of Publication2001
AuthorsHirsch, CS, Toossi, Z, Johnson, JL, Luzze, H, Ntambi, L, Peters, P, McHugh, M, Okwera, A, Joloba, M, Mugyenyi, P, Mugerwa, RD, Terebuh, P, Ellner, JJ
JournalThe Journal of infectious diseases
Volume183
Issue5
Pagination779-88
Date Published2001 Mar 1
ISSN0022-1899
KeywordsAdolescent, Adult, AIDS-Related Opportunistic Infections, Apoptosis, CD4 Lymphocyte Count, Cells, Cultured, Cytokines, Fas Ligand Protein, Female, Humans, Interferon-gamma, Leukocytes, Mononuclear, Male, Membrane Glycoproteins, Middle Aged, Mycobacterium tuberculosis, T-Lymphocytes, Tuberculosis, Pleural, Tumor Necrosis Factor-alpha, Uganda
Abstract

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.

Alternate JournalJ. Infect. Dis.
Full Text
PubMed ID11181155
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