CYCLOSPORINE-A INHIBITS 2-CHLOROADENOSINE-INDUCED DNA CLEAVAGE IN MOUSE THYMOCYTES

Incubation of mouse thymocytes with the adenosine analogue 2-chloroade nosine resulted in enhanced internucleosomal DNA fragmentation which c ould be inhibited by the immunosuppressive drug cyclosporin A. In orde r to be effective, cyclosporin A had to be added to thymocyte preparat ions at the same time as 2-chloroadenosine. Since cyclosporin A is a s elective inhibitor of calcineurin, our data suggest a possible role fo r calcineurin as a signaling intermediate in the apoptotic pathway act ivated in thymocytes through adenosine receptors. However, at the pres ent time we cannot exclude the possibility that the inhibitory effect of cyclosporin A on 2-chloroadenosine-induced apoptosis may be mediate d through a calcineurin-independent process.