SPONTANEOUS APOPTOSIS IN HUMAN THYMOCYTES

Apoptosis seems to be involved in different stages of immune cell deve lopment. In particular, experimental evidence suggests that it is a ma jor form of cell death in the thymus. The present analysis of human th ymocytes reveals that a fraction of these cells, cultured in vitro, un dergoes spontaneous apoptosis, This observation is based both on molec ular CDNA fragmentation) and morphological (electron microscopic) inve stigations of the cells. The apoptotic thymocytes are CD3(-) or CD3(10 ), CD4(10), and CD8(10) and do not express Bcl-2 protein. Furthermore, thymocytes die by apoptosis when exposed to pharmacological stimuli, such as tumor necrosis factor-alpha, dexamethasone, ATP, or Ca++ ionop hore. Thus the apoptotic machinery In thymocytes can be triggered by a n imbalance in growth factors in the in vitro culture media and can be modulated by various biochemical signals. The process of spontaneous apoptosis is independent of mRNA or protein synthesis, as actinomycin D and cycloheximide fail to inhibit this phenomenon. Furthermore, apop tosis seems to require active oxidative phosphorylation, as it is prev ented by incubation of the cells with inhibitors of the respiratory ch ain.