B7 BLOCKADE PREVENTS ACTIVATION-INDUCED CELL-DEATH OF THYMOCYTES

Although both B7 and its counter-receptor CD28 are expressed in the th ymus, the role of B7 in thymic selection is not clear. We investigated the role of B7 in intrathymic deletion of antigen-specific T cells us ing a TCR transgenic model specific for antigen ovalbumin (OVA) and H- 2A(d). Intraperitoneal injection of OVA induced apoptosis of thymocyte s and drastic reduction of thymocyte numbers. This was significantly i nhibited by co-injection of CTLA-4-Ig which blocks B7 co-stimulation. Deletion of T cells in the thymus following i.p. injection of OVA was associated with T cell pre-activation as demonstrated by T cell prolif eration and cytokine production. Injection of CTLA-4-Ig blocked all th ese activation events and rescued thymocytes from activation-induced c ell death. These results demonstrate that B7 is required for the activ ation-induced cell death of MHC class II-restricted thymocytes in vivo .