THROMBOXANE-A2 RECEPTOR IS HIGHLY EXPRESSED IN MOUSE IMMATURE THYMOCYTES AND MEDIATES DNA FRAGMENTATION AND APOPTOSIS

We have recently revealed that the thymus is the organ showing the hig hest expression of thromboxane (TX) A2 receptor in mice. In this study , thymic cell populations expressing the receptor were identified, and the effects of a TXA2 agonist on these cells were examined. Radioliga nd binding using a TXA2 receptor-specific radioligand revealed a singl e class of binding sites in the thymocytes with an affinity and specif icity identical to those reported for the TXA2 receptor. The receptor density in these cells was comparable to that seen in blood platelets. This receptor is most highly expressed in CD4-8- and CD4+8+ immature thymocytes, followed by CD4+8- and CD4-8+ cells. The receptor density in splenic T cells was less than one fifth of that in CD4+8+ cells and no binding activity was detectable in splenic B cells. The addition o f a TXA2 agonist, STA2, to thymocytes induced the disappearance of the CD4+8+ cells in a time- and concentration-dependent manner and caused DNA fragmentation. These changes were blocked by a specific TXA2 anta gonist, S-145. These results demonstrate that TXA2 induces apoptotic c ell death in immature thymocytes by acting on the TXA2 receptor on the ir cell surface and suggest a role for the TXA2/TXA2 receptor system i n the thymic micro-environment.