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(-)a nd 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 control s (n = 25). Compared with healthy controls, CD4 and CD8 T cells from patien ts with HIV and/or PTB expressed more activation markers (HLA-DR, CD38); th eir CD8 T cells expressed more CD95 (pre-apoptosis) and less CD28 (co-stimu latory receptor). Peripheral blood mononuclear cells (PBMC) of patients wit h either HIV or PTB were impaired in interferon-gamma (IFN-gamma) productio n upon antigenic stimulation. PTB (with or without HIV) was characterized b y monocytosis, granulocytosis, increased transforming growth factor-beta 1 production and PPD-induced apoptosis. In vivo CD4 T cell depletion, in vitr o increased spontaneous CD4 T cell apoptosis and defects in IFN-gamma respo nses upon mitogenic stimulation were restricted to HIV+ subjects (with or w ithout PTB). Overlapping and distinctive immune alterations, associated wit h PTB and HIV, might explain mutual unfavourable influences of both disease s.