T cell activation, apoptosis and cytokine dysregulation in the (co)pathogenesis of HIV and pulmonary tuberculosis (TB).
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-gamma) 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-gamma 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.
Hertoghe
T
T
Institute of Tropical Medicine, Department of Microbiology, Antwerp and Department of Physiology and Pathology, Free University of Brussels (VUB), Brussels, Belgium.
Wajja
A
A
Ntambi
L
L
Okwera
A
A
Aziz
M A
MA
Hirsch
C
C
Johnson
J
J
Toossi
Z
Z
Mugerwa
R
R
Mugyenyi
P
P
Colebunders
R
R
Ellner
J
J
Vanham
G
G
D017088:AIDS-Related Opportunistic Infections / Q000097:blood / Q000276:immunology* / Q000821:virology; D000293:Adolescent; D000328:Adult; D017209:Apoptosis / Q000276:immunology*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D002455:Cell Division; D002478:Cells, Cultured; D016207:Cytokines; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D008934:Mitogens / Q000276:immunology / Q000494:pharmacology; D011043:Pokeweed Mitogens / Q000276:immunology / Q000494:pharmacology; D013183:Sputum / Q000276:immunology / Q000382:microbiology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*; D053773:Transforming Growth Factor beta1; D014373:Tuberculin / Q000276:immunology / Q000494:pharmacology; D014397:Tuberculosis, Pulmonary / Q000097:blood / Q000276:immunology* / Q000821:virology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D014454:Uganda
D016207:Cytokines; D008934:Mitogens; D011043:Pokeweed Mitogens; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014373:Tuberculin; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma