Augmentation of apoptosis and interferon-gamma production at sites of active Mycobacterium tuberculosis infection in human tuberculosis.
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.
Hirsch
C S
CS
Case Western Reserve University, University Hospitals of Cleveland, Dept. of Medicine, Division of Infectious Diseases, Cleveland, OH 44106-4984, USA. cxh40@po.cwru.edu
Toossi
Z
Z
Johnson
J L
JL
Luzze
H
H
Ntambi
L
L
Peters
P
P
McHugh
M
M
Okwera
A
A
Joloba
M
M
Mugyenyi
P
P
Mugerwa
R D
RD
Terebuh
P
P
Ellner
J J
JJ
D017088:AIDS-Related Opportunistic Infections / Q000097:blood / Q000276:immunology* / Q000821:virology; D000293:Adolescent; D000328:Adult; D017209:Apoptosis / Q000276:immunology*; D018791:CD4 Lymphocyte Count; D002478:Cells, Cultured; D016207:Cytokines; D053222:Fas Ligand Protein; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000276:immunology; D007963:Leukocytes, Mononuclear; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000821:virology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D014396:Tuberculosis, Pleural / Q000097:blood / Q000276:immunology* / Q000821:virology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D014454:Uganda
D016207:Cytokines; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma