Protein synthesis dependent and independent apoptosis of murine splenic T cells

To elucidate the mechanism of apoptosis in matured T cells, we examined the effect of phorbol esters capable of activating protein kinase C, cAMP agonists, calcium ionophores, and dexamethasone on apoptosis in mouse splenic T cells. All of these agents induced apoptosis in thymocytes. Neither phorbol esters nor calcium ionophores induced apoptosis in the splenic T cells. Dibutyrylcyclic AMP induced apoptosis in splenic T cells but to a lesser extent than that in thymocytes. The results suggest that matured T cells are more resistant to various apoptogenic stimuli than thymocytes. Dexamethasone induced apoptotic cell death in splenic T cells as well as in thymocytes. Cycloheximide, an inhibitor of protein synthesis which completely inhibited thymocyte apoptosis, induced slight apoptosis in splenic T cells, but it inhibited the dexamethasone-induced apoptosis to a level at which cycloheximide induced apoptosis, indicating that at least two pathways of apoptosis exist in peripheral T cells; one protein synthesis dependent and the other independent. Taken together, the results suggest that the apoptosis of peripheral T cells is regulated by a mechanism different from that of thymocytes.