Caspase-independent apoptotic pathways in T lymphocytes: A minireview

Cell death by apoptosis is involved in the maintenance of T cell receptor d iversity, self tolerance, and T-cell number homeostasis. Until recently, ap optosis was thought to require caspase activation. Evidence is now accumula ting that a caspase-independent pathway exists, shown by in vitro experimen ts with broad-range caspase inhibitors. Mature T lymphocytes readily underg o caspase-independent apoptosis in vitro, and recent data suggest that this type of apoptosis may be involved in the negative selection of thymocytes. Mitochondria likely release death triggers specific for both caspase-depen dent and caspase-independent apoptotic pathways (cytochrome c and AIF respe ctively) in response to apoptotic stimuli. A caspase-independent pathway is triggered first in activated T lymphocytes subjected to apoptotic stimuli that do not rely on receptors with death domains. In this pathway, the earl y commitment phase to apoptosis involves cell shrinkage, peripheral DNA con densation and the translocation of mitochondrial AIF to the cytosol and nuc leus. This process is reversible until mitochondrial cytochrome c is releas ed and Delta Psi (m) dissipated. Only at this stage are caspases activated.