Regulation and Mechanisms of Apoptosis in T Lymphocytes

Abstract

Apoptotic cell death is now widely recognised as being a distinct process of importance in both normal physiology and pathology. It is characterised by morphological and biochemical changes in most cell compartments (Kerr et al., 1972; Wyllie et al., 1980). The microscopically observed nuclear alterations such as marginatiom and condensation of chromatin and nuclear fragmentation are accompanied by sequential degradation of the DNA, first into fragments of approximately 700, 300 and 50 kilobasepairs and then into small oligonucleosomal fragments which are multiples of about 200 basepairs. This multi-step process can be readily visualised by appropriate electrophoresis of DNA (Walker et al., 1995). Most cell types also show a remarkable shrinkage presumably due to the loss of water and electrolytes and the cytoplasm gradually becomes more electron dense. The plasma membrane remains remarkably intact, though it blebs and the phospholipids redistribute. The specific translocation of phosphatidylserine to the outer leaflet of the plasma membrane has been shown to play a very important role in the recognition of apoptotic cells by phagocytes (Martin et al., 1995). In addition, other membrane changes have been reported to contribute in the specific recognition and removal of the apoptotic bodies that remain after fragmentation of the dead cell (Savill et al., 1993). In this final stage of the process, the dying cells do usually not spill their contents into the extracellular space and consequently the potential for inflammation is limited.