Apoptotic Pathways Triggered By HIV and Consequences on T Cell Homeostasis and HIV-Specific Immunity

HIV infects cells of the immune system and the hallmark of HIV infection is the progressive destruction of the CD4 T lymphocyte subset. Shortly after this syndrome was reported, it was discovered that the HIV envelope could bind to the CD4 receptor, that HIV could replicate within human CD4 T cells in vitro and kill them, and that circulating CD4 T cells decreased in number as disease progressed. Mature CD4 T helper cells are key effectors in coordinating cellular and humoral immunity against pathogens, since they synthesize cytokines required for the induction of innate immunity involved in early killing of virus-infected cells, the maturation of B lymphocyte producers of neutralizing antibodies, and the differentiation of virus-specific CD8+ killer T cells (CTL). In addition, they are a source of chemokines which control the migration of lymphocytes to the site of infection and also inhibit HIV entry into CD4expressing targets. Therefore, HIV-dependent destruction of CD4 T lymphocytes is responsible for inefficient immune control of HIV replication and for the development of severe immune deficiency that leads to opportunistic infections, neurological impairment, malignancies, and ultimately death (Levy 1998).